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Last Updated :2024/07/25

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Master

Affiliation (Master)

  • Faculty of Advanced Life Science　Advanced Transdisciplinary Science　Chemical Biology

Affiliation (Master)

  • Faculty of Advanced Life Science　Advanced Transdisciplinary Science　Chemical Biology

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Profile and Settings

Affiliation

  • Hokkaido University, Frontier Research Center for Post-Genome Science and Technology, Director

Degree

  • Doctor of Science（Hokkaido University）

Profile and Settings

  • Name (Japanese)

    Monde

  • Name (Kana)

    Kenji

  • Name

    200901036377662744

Alternate Names

Affiliation

  • Hokkaido University, Frontier Research Center for Post-Genome Science and Technology, Director

Achievement

Research Interests

  • Infertility treatment   Alzheimer's disease   Inhibitors   Glycoconjugates・lipids   Chemical Biology   Vibrational Circular Dichroism   Chirality   

Research Areas

  • Nanotechnology/Materials / Biochemistry
  • Nanotechnology/Materials / Chemical biology

Research Experience

  • 2024/04 - Today Government of Japan Secretariat of Science, Technology and Innovation Policy Senior Science and Technology Policy Fellow
  • 2024/04 - Today Hokkaido University Vice Executive Director
  • 2023/04 - Today Hokkaido University Faculty of Advanced Life Science Vice Dean
  • 2016/04 - Today Hokkaido University Faculty of Advanced Life Science Directer of Frontier Research Center for Advanced Material and Life Science
  • 2010/04 - Today Hokkaido University Faculty of Advanced Life Science Professor
  • 2023/04 - 2024/03 Hokkaido University Advisor to the president
  • 2019/04 - 2023/03 Hokkaido University Faculty of Advanced Life Science Dean
  • 2019/01 - 2023/03 理化学研究所 客員主管研究員
  • 2013/04 - 2019/03 Hokkaido Universuty Faculty of Advanced Life Science Vice Dean
  • 2013/04 - 2016/03 Hokkaido University Faculty of Advanced Life Science Directer of Post-Genome Research Center
  • 2006/04 - 2010/03 Hokkaido University Faculty of Advanced Life Science Associate Professor
  • 2001/07 - 2006/03 Hokkaido University Faculty of Science Associate Professor
  • 1996/07 - 2001/06 Tohoku University Research Associate
  • 1995/01 - 1996/06 Columbia University Research Associate
  • 1994/03 - 1995/01 Columbia University Research Associate
  • 1988/04 - 1994/03 Hokkaido University Research Associate

Education

  • 1986/04 - 1988/03  Hokkaido University  Graduate School  Division of Natural Science
  • 1984/04 - 1986/03  Hokkaido University  Graduate School  Division of Natural Science
  • 1980/04 - 1984/03  Hokkaido University  Faculty of Science  Department of Chemistry

Committee Memberships

  • 2019/05 - Today   Molecular Chirality Research Organization   board of directors
  • 2015 - Today   International Conference on Chiroptical Spectroscopy   International Scientific Committee
  • 2015 - Today   Chirality (Wiley)   Editorial Board
  • 2015 -2020   International Conference on Vibrational Optical Activity   International Steering Committee
  • 2013 -2015   15th International Conference on Chiroptical Spectroscopy   Executive Committee

Awards

  • 2018 Molecular Chirality Award
     
    受賞者: MONDE Kenji
  • 1992 第7回若い世代の特別講演賞
  • 1992 September, 1992 7th Special Lecture Award for the younger generation (The Chemical Society of Japan)

Published Papers

  • Shotaro Hirota, Yusuke Ito, Shiro Inoue, Naoki Kitaoka, Tohru Taniguchi, Kenji Monde, Kosaku Takahashi, Hideyuki Matsuura
    Journal of Natural Products 87 (5) 1358 - 1367 0163-3864 2024/04 [Refereed]
  • Mahadeva M. M. Swamy, Yuta Murai, Kenji Monde, Setsuko Tsuboi, Aravind K. Swamy, Takashi Jin
    ACS Applied Materials Interfaces 1944-8244 2024/04 [Refereed]
  • Hiroko Ikushiro, Takumi Honda, Yuta Murai, Taiki Murakami, Aya Takahashi, Taiki Sawai, Haruna Goto, Shin-ichi Ikushiro, Ikuko Miyahara, Yoshio Hirabayashi, Nobuo Kamiya, Kenji Monde, Takato Yano
    Journal of Biological Chemistry 300 (3) 105728 - 105728 0021-9258 2024/03 [Refereed]
  • Shotaro Nagami, Rintaro Kaguchi, Taichi Akahane, Yu Harabuchi, Tohru Taniguchi, Kenji Monde, Satoshi Maeda, Satoshi Ichikawa, Akira Katsuyama
    Nature Chemistry 1755-4330 2024/02/28 [Refereed]
  • Determination of N -centered stereochemistry in N22-methylated chlorophyll- a derivatives and their epimer-dependent optical spectra
    Riko Ataka, Tohru Taniguchi, Kenji Monde, Hitoshi Tamiaki
    Chirality in press  2024 [Refereed]
  • Sajeer Koolath, Yuta Murai, Tomoya Suzuki, Mahadeva M. M. Swamy, Seigo Usuki, Kenji Monde
    ACS Medicinal Chemistry Letters 14 (9) 1237 - 1241 1948-5875 2023/08 [Refereed]
  • Hiroko Ikushiro, Taiki Murakami, Aya Takahashi, Asuka Katayama, Taiki Sawai, Haruna Goto, Sajeer Koolath, Yuta Murai, Kenji Monde, Ikuko Miyahara, Nobuo Kamiya, Takato Yano
    Journal of Biological Chemistry 299 (5) 104684 - 104684 0021-9258 2023/05 [Refereed]
  • Mariam Abdelrasoul, Kohei Yuyama, Mahadeva M. M. Swamy, Yuta Murai, Kenji Monde
    Chirality 35 (9) 577 - 585 0899-0042 2023/04 [Refereed]
     
    Abstract Stereochemistry has a substantial impact on the biological activity of various drugs. We investigated the role of stereochemistry of ceramides in inducing the production of exosomes, a type of extracellular vesicle, from neuronal cells, with a potential benefit in improving the clearance of amyloid‐β (Aβ), a causal agent of Alzheimer's disease. A stereochemical library of diverse ceramides with different tail lengths was synthesized with the purpose of varying stereochemistry (D‐erythro: DE, D‐threo: DT, L‐erythro: LE, L‐threo: LT) and hydrophobic tail length (C6, C16, C18, C24). The exosome levels were quantified using TIM4‐based exosome enzyme‐linked immunosorbent assay after concentrating the conditioned medium using centrifugal filter devices. The results revealed a pivotal role of stereochemistry in determining the biological activity of ceramide stereoisomers, with the superiority of those based on DE and DT stereochemistry with C16 and C18 tails, which demonstrated significantly higher exosome production, without a significant change in the particle size of the released exosomes. In transwell experiments with Aβ‐expressed neuronal and microglial cells, DE‐ and DT‐ceramides with C16 and C18 tails significantly decreased extracellular Aβ levels. The results reported here are promising in the design of non‐classic therapies for the treatment of Alzheimer's disease.
  • Akane Yamagishi, Yuki Egoshi, Makoto T. Fujiwara, Noriyuki Suzuki, Tohru Taniguchi, Ryuuichi D. Itoh, Yumiko Suzuki, Yoshiro Masuyama, Kenji Monde, Toyonobu Usuki
    Chemistry – A European Journal 0947-6539 2022/11 [Refereed]
  • Bojan P. Bondzić, Konstantinos Daskalakis, Tohru Taniguchi, Kenji Monde, Yujiro Hayashi
    Organic Letters 24 (40) 7455 - 7460 1523-7060 2022/10 [Refereed]
  • Kohei Yuyama, Hui Sun, Yasuyuki Igarashi, Kenji Monde, Takumi Hirase, Masato Nakayama, Yoichi Makino
    Alzheimer's research & therapy 14 (1) 140 - 140 2022/10 [Refereed]
     
    BACKGROUND: The protracted preclinical stage of Alzheimer's disease (AD) provides the opportunity for early intervention to prevent the disease; however, the lack of minimally invasive and easily detectable biomarkers and their measurement technologies remain unresolved. Extracellular vesicles (EVs) are nanosized membrane vesicles released from a variety of cells and play important roles in cell-cell communication. Neuron-derived and ganglioside-enriched EVs capture amyloid-ß protein, a major AD agent, and transport it into glial cells for degradation; this suggests that EVs influence Aß accumulation in the brain. EV heterogeneity, however, requires the use of a highly sensitive technique for measuring specific EVs in biofluid. In this study, immuno-digital invasive cleavage assay (idICA) was developed for quantitating target-intact EVs. METHODS: EVs were captured onto ganglioside GM1-specific cholera toxin B subunit (CTB)-conjugated magnetic beads and detected with a DNA oligonucleotide-labeled Aß antibody. Fluorescence signals for individual EVs were then counted using an invasive cleavage assay (ICA). This idICA examines the Aß-bound and GM1-containing EVs isolated from the culture supernatant of human APP-overexpressing N2a (APP-N2a) cells and APP transgenic mice sera. RESULTS: The idICA quantitatively detected Aß-bound and GM1-containing EVs isolated from culture supernatants of APP-N2a cells and sera of AD model mice. The idICA levels of Aß-associated EVs in blood gradually increased from 3- to 12-month-old mice, corresponding to the progression of Aß accumulations in the brain of AD model mice. CONCLUSIONS: The present findings suggest that peripheral EVs harboring Aß and GM1 reflect Aß burden in mice. The idICA is a valuable tool for easy quantitative detection of EVs as an accessible biomarker for preclinical AD diagnosis.
  • Yuta Murai, Takumi Honda, Kohei Yuyama, Daisuke Mikami, Koichi Eguchi, Yuichi Ukawa, Seigo Usuki, Yasuyuki Igarashi, Kenji Monde
    International Journal of Molecular Sciences 23 (18) 10751 - 10751 2022/09 [Refereed]
     
    The extracellular accumulation of aggregated amyloid-β (Aβ) in the brain leads to the early pathology of Alzheimer’s disease (AD). The administration of exogenous plant-type ceramides into AD model mice can promote the release of neuronal exosomes, a subtype of extracellular vesicles, that can mediate Aβ clearance. In vitro studies showed that the length of fatty acids in mammalian-type ceramides is crucial for promoting neuronal exosome release. Therefore, investigating the structures of plant ceramides is important for evaluating the potential in releasing exosomes to remove Aβ. In this study, we assessed plant ceramide species with D-erythro-(4E,8Z)-sphingadienine and D-erythro-(8Z)-phytosphingenine as sphingoid bases that differ from mammalian-type species. Some plant ceramides were more effective than mammalian ceramides at stimulating exosome release. In addition, using deuterium chemistry-based lipidomics, most exogenous plant ceramides were confirmed to be derived from exosomes. These results suggest that the ceramide-dependent upregulation of exosome release may promote the release of exogenous ceramides from cells, and plant ceramides with long-chain fatty acids can effectively release neuronal exosomes and prevent AD pathology.
  • Yuta Murai, Kohei Yuyama, Daisuke Mikami, Yasuyuki Igarashi, Kenji Monde
    Chemistry and Physics of Lipids 245 105202 - 105202 0009-3084 2022/07 [Refereed]
     
    The use of deuterium-incorporated bioactive compounds is an efficient method for tracing their metabolic fate and for quantitative analysis by mass spectrometry without complicated HPLC separation even if their amounts are extremely small. Plant sphingolipids and their metabolites, which have C4, 8-olefins on a common backbone as a sphingoid base, show unique and fascinating bioactivities compared to those of sphingolipids in mammals. However, the functional and metabolic mechanisms of exogenous plant sphingolipids have not been elucidated due to the difficulty in distinguishing exogenous sphingolipids from endogenous sphingolipids having the same polarity and same molecular weight by mass spectrometric analysis. Their roles might be elucidated by the use of deuterated probes with original biological and physicochemical properties. In this study, we designed (2S,3R,4E,8Z)-2-aminooctadeca-4,8-diene-17,17,18,18,18-d5-1,3-diol (penta-deuterium-labeled 4E, 8Z-sphingadienine) as a tracer for exogenous metabolic studies. In addition, the sphingadienine was confirmed to be metabolized in HEK293 cells and showed distinct peaks in mass spectrometric analysis.
  • Santanu Mondal, Ravindra D. Aher, Venkati Bethi, Yu-Ju Lin, Tohru Taniguchi, Kenji Monde, Fujie Tanaka
    Organic Letters 24 (9) 1853 - 1858 1523-7060 2022/03 [Refereed]
  • Yuta Murai, Akihiro Sekiguchi, Taeko Hirakawa, Seigo Usuki, Yasuyuki Igarashi, Kenji Monde
    Chirality 34 807 - 812 0899-0042 2022/02 [Refereed]
  • Mahadeva M. M. Swamy, Mohamad Zarif Mohd Zubir, Mutmainah, Setsuko Tsuboi, Yuta Murai, Kenji Monde, Ken-ichi Hirano, Takashi Jin
    The Analyst 147 (19) 4206 - 4212 0003-2654 2022 [Refereed]
     
    A near infrared fluorescence labelled long-chain fatty acid (FFA), Alexa680-BMPP (BMPP: 15-(4-(3-aminopropyl)phenyl)-3-methyl pentadecanoic acid), was synthesized as a fluorescent probe toward optical imaging of cardiac metabolism.
  • Mahadeva M. M. Swamy, Setsuko Tsuboi, Yuta Murai, Kenji Monde, Takashi Jin
    RSC Advances 12 (30) 19632 - 19639 2022 [Refereed]
     
    The labelling of annexin V with indocyanine green (ICG) and π-conjugation extended ICG (ICG-C11) resulted in SWIR emitting probes that enable high-contrast molecular imaging of tumor apoptosis in living mice.
  • Tohru Taniguchi, Naka Ida, Takuya Kitahara, Davidson Obinna Agbo, Kenji Monde
    Chemical Communications 58 (41) 6116 - 6119 1359-7345 2022 [Refereed]
     
    Using VCD spectroscopy to elucidate absolute configuration and conformational preferences of hydroxy fatty acids, lipid epoxides, and lipid hydroperoxides.
  • Mohamad Zarif Mohd Zubir, Nurul Fajry Maulida, Yoshihiro Abe, Yuta Nakamura, Mariam Abdelrasoul, Tohru Taniguchi, Kenji Monde
    Organic & Biomolecular Chemistry 20 (5) 1067 - 1072 1477-0520 2022 [Refereed]
     
    Methoxy-d3 group installed at the C-1 position of a series of epimeric pairs of sugars generated mirror-image VCD patterns in the 2300–1900 cm−1 region depending on the C-1 stereochemistry irrespective of the configurations at other positions.
  • Nariyoshi Umekubo, Tohru Taniguchi, Kenji Monde, Yujiro Hayashi
    Asian Journal of Organic Chemistry 10 (12) 3261 - 3265 2193-5807 2021/12 [Refereed]
  • Tohru Taniguchi, Mohamad Zarif Mohd Zubir, Nobuyuki Harada, Kenji Monde
    Physical Chemistry Chemical Physics 23 (48) 27525 - 27532 1463-9076 2021/11 [Refereed]
     
    Introduction of chromophores in the 2300–2000 cm−1 region such as nitrile and azido groups yields strong VCD signals whose shapes are indicative of molecular structures, as studied by experimental work and theoretical calculations.
  • Seitaro Koshino, Tohru Taniguchi, Kenji Monde, Eunsang Kwon, Yujiro Hayashi
    Chemistry – A European Journal 27 (63) 15786 - 15794 0947-6539 2021/11 [Refereed]
  • Mahadeva M. M. Swamy, Yuta Murai, Kenji Monde, Setsuko Tsuboi, Takashi Jin
    Bioconjugate Chemistry 32 (8) 1541 - 1547 1043-1802 2021/08/18 [Refereed]
     
    Recently, shortwave-infrared (SWIR) fluorescence imaging for the optical diagnostics of diseases has attracted much attention as a new noninvasive imaging modality. For this application, the development of SWIR molecular imaging probes with high biocompatibility is crucial. Although many types of biocompatible SWIR fluorescent probes based on organic dyes have been reported, there are no SWIR-emitting molecular imaging probes that can be used for the detection of specific biomolecules in vivo. To apply SWIR-emitting molecular imaging probes to biomedical fields, we developed a biocompatible SWIR fluorescent dye based on π-conjugation extended indocyanine green (ICG), where ICG is the only approved near-infrared dye by the US Food and Drug Administration (FDA) for use in the clinic. Using the π-conjugation extended ICG, we prepared SWIR molecular imaging probes that can be used for in vivo tumor imaging. Herein, we demonstrate noninvasive SWIR fluorescence imaging of human epidermal growth factor receptor 2 (HER2)-positive and epidermal growth factor receptor (EGFR)-positive breast tumors using π-conjugation extended ICG and monoclonal antibody conjugates. The presented π-conjugation extended ICG analog probes will be a breakthrough to apply SWIR fluorescence imaging in biomedical fields.
  • こんにゃく由来グルコシルセラミド摂取による脳内アミロイドβ蓄積に対する抑制効果の探索的試験－プラセボ対照ランダム化二重盲検並行群間比較試験－
    江口 晃一, 向井 克之, 湯山 耕平, 栗本 成敬, 田中 藍子, 勝山(鏡) 豊代, 西平 順, 門出 健次, 五十嵐 靖之
    薬理と治療 49 (8) 1225 - 1239 2021 [Refereed]
  • Hadya Virupaksha Deepak, Mahadeva M. M. Swamy, Yuta Murai, Yoshiko Suga, Masaki Anetai, Takuro Yo, Masahiro Kuragano, Koji Uwai, Kiyotaka Tokuraku, Kenji Monde
    Molecules 25 (18) 4077 - 4088 2020/09 [Refereed][Not invited]
     
    Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb “Manshanfong” used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum, is a meroterpenoid with antibacterial, anti-HIV, and anti-inflammatory activities. However, the mechanisms underlying these pharmacologic activities are poorly understood. To develop new drugs based on DCA, more information is required regarding its interactions with biomolecules. The present study showed that DCA inhibits the activity of the enzyme sphingomyelin synthase, with an IC50 of 4 µM. The structure–activity relationships between DCA and sphingomyelin synthase were evaluated using derivatives and cyclized hongoquercin A. In addition, DCA was found to inhibit amyloid β aggregation. These results may help in the design of effective drugs based on DCA.
  • Seitaro Koshino, Akira Takikawa, Keiichi Ishida, Tohru Taniguchi, Kenji Monde, Eunsang Kwon, Shigenobu Umemiya, Yujiro Hayashi
    Chemistry – A European Journal 26 (20) 4524 - 4530 0947-6539 2020/04/06 [Refereed][Not invited]
  • Enkhsukh Lkhamkhuu, Kazunori Zikihara, Hitomi Katsura, Satoru Tokutomi, Takafumi Hosokawa, Yoshihisa Usami, Mitsuyoshi Ichihashi, Junji Yamaguchi, Kenji Monde
    Plant Biotechnology 37 (1) 57 - 67 1342-4580 2020/03/25 [Refereed][Not invited]
     
    Circular dichroism (CD), defined as the differential absorption of left- and right-handed circularly polarized light (CPL), is a useful spectroscopic technique for structural studies of biological systems composed of chiral molecules. The present study evaluated the effects of CPL on germination, hypocotyl elongation and biomass production of Arabidopsis and lettuce. Higher germination rates were observed when Arabidopsis and lettuce seedlings were irradiated with red right-handed CPL (R-CPL) than with red left-handed CPL (L-CPL). Hypocotyl elongation was effectively inhibited when Arabidopsis and lettuce seedlings were irradiated with red R-CPL than with red L-CPL. This difference was not observed when a phytochrome B (phyB) deficient mutant of Arabidopsis was irradiated, suggesting that inhibition of elongation by red R-CPL was mediated by phyB. White R-CPL induced greater biomass production by adult Arabidopsis plants, as determined by their fresh shoot weight, than white L-CPL. To determine the molecular basis of these CPL effects, CD spectra and the effect of CPL on the photoreaction of a sensory module of Arabidopsis phyB were measured. The red light-absorbing form of phyB showed a negative CD in the red light-absorbing region, consistent with the results of germination, inhibition of hypocotyl elongation and biomass production. L-CPL and R-CPL, however, did not differ in their ability to induce the interconversion of the red light-absorbing and far-red light-absorbing forms of phyB. These findings suggest that these CPL effects involve phyB, along with other photoreceptors and the photosynthetic process.
  • Sajeer Koolath, Yuta Murai, Yoshiko Suga, Kenji Monde
    Chirality 32 (3) 308 - 313 2020/03 [Refereed][Not invited]
     
    Enantiomers or diastereomers of chiral bioactive compounds often exhibit different biological and toxicological properties. Here, we report the efficient synthesis of four stereoisomers of sphingosine and derivatization of unique chiral ceramides through a combinatorial chemistry by solid-phase activated resin ester. In addition, to test the effectivity of stereochemistry of ceramide, we demonstrated a cell-based assay of sphingomyelin synthase inhibition in the presence ofchiral unique ceramides, which suggested that libraries of this sort will be a rich source of biologically active synthetic molecules.
  • Seigo Usuki, Yoshiaki Yasutake, Noriko Tamura, Tomohiro Tamura, Kunikazu Tanji, Takashi Saitoh, Yuta Murai, Daisuke Mikami, Kohei Yuyama, Kenji Monde, Katsuyuki Mukai, Yasuyuki Igarashi
    Cells 9 (2) 2020/02/24 [Refereed][Not invited]
     
    Konjac ceramide (kCer) is a plant-type ceramide composed of various long-chain bases and a-hydroxyl fatty acids. The presence of d4t,8t-sphingadienine is essential for semaphorin 3A (Sema3A)-like activity. Herein, we examined the three neuropilin 1 (Nrp1) domains (a1a2, b1b2, or c), and found that a1a2 binds to d4t,8t-kCer and possesses Sema3A-like activity. kCer binds to Nrp1 with a weak affinity of mM dissociation constant (Kd). We wondered whether bovine serum albumin could influence the ligand-receptor interaction that a1a2 has with a single high affinity binding site for kCer (Kd in nM range). In the present study we demonstrated the influence of bovine serum albumin. Thermal denaturation indicates that the a1a2 domain may include intrinsically disordered region (IDR)-like flexibility. A potential interaction site on the a1 module was explored by molecular docking, which revealed a possible Nrp1 activation mechanism, in which kCer binds to Site A close to the Sema3A-binding region of the a1a2 domain. The a1 module then accesses a2 as the IDR-like flexibility becomes ordered via kCer-induced protein rigidity of a1a2. This induces intramolecular interaction between a1 and a2 through a slight change in protein secondary structure.
  • Saaidin S. A., Murai, Y., Ishikawa, T., Monde, K.
    Eur. J. Org. Chem. 2019 (46) 7563 - 7567 2019/12 [Refereed][Not invited]
  • Muhamad Aqmal Othman, Kohei Yuyama, Yuta Murai, Yasuyuki Igarashi, Daisuke Mikami, Yasodha Sivasothy, Khalijah Awang, Kenji Monde
    ACS medicinal chemistry letters 10 (8) 1154 - 1158 2019/08/08 [Refereed][Not invited]
     
    The interaction between natural occurring inhibitors and targeted membrane proteins could be an alternative medicinal strategy for the treatment of metabolic syndrome, notably, obesity. In this study, we identified malabaricones A-C and E (1-4) isolated from the fruits of Myristica cinnamomea King as natural inhibitors for sphingomyelin synthase (SMS), a membrane protein responsible for sphingolipid biosynthesis. Having the most promising inhibition, oral administration of compound 3 exhibited multiple efficacies in reducing weight gain, improving glucose tolerance, and reducing hepatic steatosis in high fat diet-induced obesity mice models. Liver lipid analysis revealed a crucial link between the SMS activities of compound 3 and its lipid metabolism in vitro and in vivo. The nontoxic nature of compound 3 makes it a suitable candidate in search of drugs which can be employed in the treatment and prevention of obesity.
  • Hironori Okamura, Takanobu Fujioka, Naoki Mori, Tohru Taniguchi, Kenji Monde, Hidenori Watanabe, Hirosato Takikawa
    Tetrahedron Letters 60 (32) 150917 - 150917 0040-4039 2019/08 [Refereed][Not invited]
  • Rina Sasaki, Reina Tainaka, Yuichi Ando, Yurika Hashi, Hadya V Deepak, Yoshiko Suga, Yuta Murai, Masaki Anetai, Kenji Monde, Kiminori Ohta, Ikuko Ito, Haruhisa Kikuchi, Yoshiteru Oshima, Yasuyuki Endo, Hitomi Nakao, Masafumi Sakono, Koji Uwai, Kiyotaka Tokuraku
    Scientific reports 9 (1) 2587 - 2587 2019/02 [Refereed][Not invited]
     
    Protein aggregation is the principal component of numerous protein misfolding pathologies termed proteinopathies, such as Alzheimer's disease, Parkinson's disease, prion disease, and AA amyloidosis with unmet treatment needs. Protein aggregation inhibitors have great potential for the prevention and treatment of proteinopathies. Here we report the development of an automated real-time microliter-scale high throughput screening (MSHTS) system for amyloid aggregation inhibitors using quantum-dot nanoprobes. Screening 504 crude extracts and 134 low molecular weight aromatic compounds revealed the relationship of amyloid-β (Aβ) aggregation inhibitory activities of plant extracts using a plant-based classification. Within the eudicots, rosids, Geraniales and Myrtales showed higher activity. Screening low molecular weight aromatic compounds demonstrated that the structure of tropolone endows it with potential Aβ aggregation inhibitory activity. The activity of the most active tropolone derivative was higher than that of rosmarinic acid. MSHTS also identified three chaperone molecules as tau aggregation inhibitors. These results demonstrate that our automated MSHTS system is a novel and robust tool that can be adapted to a wide range of compounds and aggregation-prone polypeptides.
  • Kiske, C, Riegel, A, Hopf, R, Kvindt, A, Poplacean, I, Taniguchi, T, Swamy, M, Monde, K, Eisenreich, W, Engel, K
    J. Agric. Food Chem. 67 (4) 1187 - 1196 2019/01 [Refereed][Not invited]
  • Mahadeva M M Swamy, Yuta Murai, Yusuke Ohno, Keisuke Jojima, Akio Kihara, Susumu Mitsutake, Yasuyuki Igarashi, Jian Yu, Min Yao, Yoshiko Suga, Masaki Anetai, Kenji Monde
    Chemical communications (Cambridge, England) 54 (90) 12758 - 12761 2018/11/08 [Refereed][Not invited]
     
    Ginkgolic acid obtained as a sphingomyelin synthase inhibitor from a plant extract library inspired the concept of sphingolipid mimics. Ginkgolic acid-derived N-acyl anilines and ginkgolic acid 2-phosphate (GA2P) respectively mimic ceramide and sphingosine 1-phosphate (S1P) in structure and function. The GA2P-induced phosphorylation of ERK and internalization of S1P receptor 1 (S1P1) indicated potent agonist activity. Docking studies revealed that GA2P adopts a similar binding conformation to the bound ligand ML5, which is a strong antagonist of S1P1.
  • Taniguchi, T, Suzuki, T, Satoh, H, Shichibu, Y, Konishi, K, Monde, K
    J. Am. Chem. Soc. 140 (46) 15577 - 15581 2018/11 [Refereed][Not invited]
  • Katakami, C, Kamo, S, Torii, A, Hara, N, Imai, Y, Taniguchi, T, Monde, K, Okabayashi, Y, Hosokai, T, Kuramochi, K, Tsubaki, K
    J. Org. Chem. 83 (23) 14610 - 14616 0022-3263 2018/10 [Refereed][Not invited]
     
    Both enantiomers of axially chiral bis-(dinaphthofuran) were prepared in only two steps from 1'-hydroxy-4'-methoxy-2,2'-binaphthalenyl-1,4-dione, followed by optical resolution via high-performance liquid chromatography (HPLC) using a chiral stationary phase (CSP). The absolute configurations were determined by comparison of experimental and calculated vibrational circular dichroism (VCD) spectra. Synthetic bis(dinaphthofuran) exhibited a broad and unstructured emission derived from an intramolecular excimer in both solution and solid state. The methylene bridge brings both chromophores close to each other and induces significant changes in the photophysical behavior. Chiral bis(dinaphthofuran) displayed a bathochromic shift in emission, as compared to the racemic mixture in the solid state. Furthermore, the compounds showed high circularly polarized luminescence (CPL) with a dissymmetry factor (g(lum)) of 10(-3) at 405 nm upon excitation at 265 nm in a methanol solution. This compound serves as a model for the design and synthesis of organic materials having CPL activity.
  • Murakami R, Sano K, Iwai T, Taniguchi T, Monde K, Sawamura M
    Angew. Chem., Int. Ed. 57 (30) 9465 - 9469 1433-7851 2018/07 [Refereed][Not invited]
     
    The palladium-catalyzed asymmetric side-chain C(alpha)-allylation of 2-alkylpyridines, without using an external base, was developed. The high linear selectivities and enantioselectivities were achieved using new chiral diamidophosphite monodentate ligands. Given that the reaction conditions do not require an external base, this catalyst system enabled chemoselective C(alpha)-allylation of 2-alkylpyridines containing alpha-carbonyl C-H bonds, which are more acidic than alpha-pyridyl C-H bonds.
  • Genki Kawauchi, Shigenobu Umemiya, Tohru Taniguchi, Kenji Monde, Yujiro Hayashi
    Chemistry - A European Journal 24 (33) 8409 - 8414 1521-3765 2018/06/12 [Refereed][Not invited]
     
    An enantioselective total synthesis of latanoprost was achieved. Its chiral cyclopentane core structure was constructed through an organocatalyst-mediated [3+2]-cycloaddition reaction, and chirality in the ω-side chain was generated by prolinate-anion-mediated α-aminoxylation of an aldehyde. Highly diastereoselective domino acetalization and an oxy-Michael reaction were key steps for the generation of C9 chirality.
  • Takahiro Hongen, Tohru Taniguchi, Kenji Monde
    Chirality 30 (4) 396 - 401 1520-636X 2018/04/01 [Refereed][Not invited]
     
    Oligo(lactic acid) is an ester-analogue of short oligoalanine sequence and adopts a rigid left-handed helical structure. In this study, oligo(lactic acid) was incorporated into oligoalanine sequences and their conformations were studied by vibrational circular dichroism and electronic circular dichroism spectroscopy. The results suggested that oligo(lactic acid) moiety in these sequences maintains a left-handed helix and increases the conformational propensity of the oligoalanine moiety to form a left-handed polyproline type II-like helix. The importance of the chirality of oligo(lactic acid) moiety for the oligoalanine conformation was also studied. The results obtained in this study should be useful in developing ester-containing oligopeptides that function better than normal peptides.
  • Taniguchi, T, Nakano, K, Monde, K
    Current Protocols in Nucleic Acid Chemistry 72 (1) 7.29.1 - 7.29.9 2018/03 [Refereed][Not invited]
  • Siddabasave Gowda B Gowda, Atsufumi Nakahashi, Keiko Yamane, Saori Nakahashi, Yuta Murai, Ananda Kumar C Siddegowda, Mostafa A S Hammam, Kenji Monde
    ACS omega 3 (1) 753 - 759 2018/01/31 [Refereed][Not invited]
     
    Sphingoid bases, which have a 2-amino-1,3-diol common functional group, are the structural backbone units of all sphingolipids. Recently, much attention has been focused on sphingoid bases because of their potentially beneficial bioactivities toward various cancer cells as well as their dietary interest. However, low abundance and the handling complexity caused by their amphiphilic character led to very limited research on them. Glutaraldehyde has two aldehyde groups, and it reacts rapidly with the 2-amino-1,3-diol functional group of sphingosine to give a tricyclic product. Immobilization of glutaraldehyde on a resin was successfully performed by organic synthesis, starting from trans-p-coumaric acid via eight steps. This approach suppresses the self-polymerization of glutaraldehyde, and addition of water to the developed resin causes the formation of cyclic double hemiacetal function, which avoids oxidation like a reducing sugar in nature and makes it stable even for up to 1 year incubation. The resin was applied to the solid-phase extracting experiment of free sphingosine from human serum at a concentration of 280 nM. Another extraction study of edible golden oyster mushrooms showed that the sphingoid base was selectively captured from complex natural extracts. These results demonstrate that the developed glutaraldehyde resin method is a highly selective method, and hence, the combination of it with the o-phthaldialdehyde HPLC method was confirmed as an efficient and sensitive method for analysis of sphingoid bases in biological samples.
  • Koji Narita, Hajime Sato, Atsushi Minami, Kosei Kudo, Lei Gao, Chengwei Liu, Taro Ozaki, Motoichiro Kodama, Xiaoguang Lei, Tohru Taniguchi, Kenji Monde, Mami Yamazaki, Masanobu Uchiyama, Hideaki Oikawa
    ORGANIC LETTERS 19 (24) 6696 - 6699 1523-7060 2017/12 [Refereed][Not invited]
     
    Heterologous expression of four Glade-A bifunctional terpene synthases (BFTSs), giving di/sesterterpenes with unique polycyclic carbon skeletons such as sesterfisherol, enabled the isolation of the sesterterpenes Bm1, Bm2, Bm3, and Ph1. Their structures suggested that formation of the products occurs via various diastereomeric carbocation intermediates, allowing the proposal that dade-A BFTSs catalyze three-step cyclizations using several stereofacial combinations of allylic cation-olefin pairs in the corresponding intermediates to generate various stereoisomers.
  • Yurie Takayama, Takaoki Ishii, Hirohisa Ohmiya, Tomohiro Iwai, Martin C. Schwarzer, Seiji Mori, Tohru Taniguchi, Kenji Monde, Masaya Sawamura
    CHEMISTRY-A EUROPEAN JOURNAL 23 (35) 8400 - 8404 0947-6539 2017/06 [Refereed][Not invited]
     
    Prolinol-phosphine chiral ligands enabled highly enantioselective copper-catalyzed intermolecular alkyne-nitrone coupling (Kinugasa reaction) to produce 1,3,4-trisubstituted chiral beta-lactams. A high level of enantiocontrol was achieved not only with aryl-or alkenylacetylenes but also with alkylacetylenes, which were important but unfavorable substrates in the previously reported protocols. Two-point hydrogen bonding between the chiral ligand and the nitrone oxyanion consisting of O-H center dot center dot center dot O and C(sp(3)) H center dot center dot center dot O hydrogen bonds is proposed.
  • Tohru Taniguchi, Kenji Monde
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 75 (5) 522 - 529 0037-9980 2017/05 [Refereed][Not invited]
     
    The use of theoretical calculations of circular dichroism (CD) and vibrational circular dichroism (VCD) spectroscopies for structural analysis has been becoming popular among organic chemists. In association with the conventional CD exciton chirality method and a recently-developed VCD exciton chirality method, proper use of CD and VCD spectroscopies should advance various studies related to chirality. This article briefly discusses the basics of structural analysis using theoretical calculations and the exciton chirality method of CD and VCD, with some tips and cautions for reliable spectral interpretation. The latter half of this article is dedicated to describing recent examples of the use of VCD for analyzing the configuration and conformation of small molecules, polymers, supramolecules, etc.
  • Ji-Rong Huang, Muhammad Sohail, Tohru Taniguchi, Kenji Monde, Fujie Tanaka
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 56 (21) 5853 - 5857 1433-7851 2017/05 [Refereed][Not invited]
     
    Spiro[4,5]decanes and polycyclic compounds bearing spiro[4,5] decane systems are important biofunctional molecules. Described are diastereoselective formal (4+1)cycloaddition reactions to afford oxindole-functionalized spiro[4,5]decanes and organocatalytic enantioselective Michael-Henry cascade reactions of the (4+1) cycloaddition products to generate spirooxindole polycyclic derivatives bearing the spiro[4,5]decane system. Spiro[4,5]decanes bearing oxindoles containing three stereogenic centers and spirooxindole polycycles having seven stereogenic centers, including two all-carbon chiral quaternary centers and one tetrasubstituted chiral carbon center, were obtained with high diastereo- and enantioselectivities.
  • Shota Saito, Yuta Murai, Seigo Usuki, Masafumi Yoshida, Mostafa A. S. Hammam, Susumu Mitsutake, Kohei Yuyama, Yasuyuki Igarashi, Kenji Monde
    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2017 (6) 1045 - 1051 1434-193X 2017/02 [Refereed][Not invited]
     
    Fluorous solid-phase extraction (FSPE) is a useful technique for efficient selective enrichment of fluorous compounds from nonfluorous molecules. Sphingolipids and their metabolites, which are ubiquitous building blocks of eukaryotic and prokaryotic cell membranes, play crucial roles, for example, as signaling molecules. However, details of the functions and metabolic mechanisms of exogenous sphingolipids have remained unknown compared with those of their endogenous analogs. To better understand these unknown roles, chemical probes with appropriate biological and physicochemical properties are needed. In this study, we designed and synthesized new fluorous sphingolipids to reveal these roles. Furthermore, we confirmed that they could be efficiently and rapidly separated from normal sphingolipids by FSPE, and that they hardly showed any cytotoxic activity, similarly to normal sphingolipids at the same dose. We also showed that these fluorinated ceramides could act as metabolic substrates for sphingomyelin synthase 2 (SMS2). This demonstrates their potential for further biological studies.
  • 化学プローブは求愛タンパク質の心をどう射留めるのか？-生命現象解明・創薬に小分子の視点から
    門出 健次, 村井 勇太
    化学 72 (10) 70 - 71 2017 [Not refereed][Not invited]
  • 谷口 透, 門出 健次
    有機合成化学協会誌 75 522 - 529 2017 [Not refereed][Not invited]
  • Tohru Taniguchi, Kie Nakano, Ryosuke Baba, Kenji Monde
    ORGANIC LETTERS 19 (2) 404 - 407 1523-7060 2017/01 [Refereed][Not invited]
     
    A reliable and convenient method for determining the configuration and conformation of the furanose ring in carbohydrates and nucleosides by vibrational circular dichroism (VCD) spectroscopy is described. Diastereomeric pairs of several furanose monosaccharides and nucleosides were prepared, and their VCD spectra were analyzed. The results revealed that VCD spectroscopy elucidates the equibrated state of the furanose ring puckers, which is often difficult to study by other techniques.
  • Koji Kasamatsu, Tomoyuki Yoshimura, Attila Mandi, Tohru Taniguchi, Kenji Monde, Takumi Furuta, Takeo Kawabata
    ORGANIC LETTERS 19 (2) 352 - 355 1523-7060 2017/01 [Refereed][Not invited]
     
    A method for asymmetric alpha-arylation of alpha-amino acid derivatives via memory of chirality has been developed. Addition of axially chiral enolates, generated from alpha-amino acid derivatives, to in situ generated arynes, followed by intramolecular C-acylation of the resulting aryl metallic species, gave benzocyclobutenones with a tetrasubstituted carbon with retention of configuration in up to 99% ee.
  • Christiane Kiske, Svenja Noerenberg, Miriam Ecker, Xingyue Ma, Tohru Taniguchi, Kenji Monde, Wolfgang Eisenreich, Karl-Heinz Engel
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 64 (45) 8563 - 8571 0021-8561 2016/11 [Refereed][Not invited]
     
    The absolute configurations of chiral beta-mercaptoalkanones were previously assigned on the basis of the H-1 NMR anisotropy method using (S)-2-methoxy-2-(1-naphthyl)propionic acid ((S)-M alpha NP) as the chiral auxiliary. This study presents a reinvestigation of the configurations of 4-mercapto-2-pentanone 1, 4-mercapto-2-heptanone 2, and 2-mercapto-4-heptanone 3. Enantiomers of 1, 2, and 3 were obtained by lipase-catalyzed hydrolyses of the respective acetylthioalkanones. Upon derivatization with (S)-M alpha NP, the configurations of the reaction products were deduced based on the order of the HPLC elution of the diastereoisomeric thioesters, assuming that the sector rule previously developed for secondary alcohols is also valid for thiols. In addition, the configurations were experimentally determined by vibrational circular dichroism (VCD) and ill NMR analyses after esterification with (R)-hydratropic acid (HTA) and 2-methoxy-2-phenylacetic acid (MPA). The assignments of the configurations using VCD and NMR analyses of HTA- and MPA-thioesters were in agreement. However, they were opposite to those deduced for (S)-M alpha NP thioesters via the sector rule. Consequently, the formerly assigned configurations of beta-mercaptoalkanones deduced via investigation of (S)-M alpha NP-derivatives have to be revised.
  • Yujiro Hayashi, Bojan P. Bondzic, Tatsuya Yamazaki, Yogesh Gupta, Shin Ogasawara, Tohru Taniguchi, Kenji Monde
    CHEMISTRY-A EUROPEAN JOURNAL 22 (44) 15874 - 15880 0947-6539 2016/10 [Refereed][Not invited]
     
    The asymmetric Diels-Alder reaction of -substituted acrolein proceeds in the presence of the trifluoroacetic acid salt of trifluoromethyl-substituted diarylprolinol silyl ether to afford the exo-isomer with both excellent diastereoselectivity and high enantioselectivity. In the Diels-Alder reaction of a ,-disubstituted ,-unsaturated aldehyde, good exo-selectivity and excellent enantioselectivity was obtained when the perchloric acid salt of the bulky triisopropyl silyl ether of trifluoromethyl substituted diarylprolinol was employed as an organocatalyst in the presence of water. In both cases, all-carbon quaternary stereocenters are constructed enantioselectively.
  • Tohru Taniguchi, Takahiro Hongen, Kenji Monde
    POLYMER JOURNAL 48 (9) 925 - 931 0032-3896 2016/09 [Refereed][Invited]
     
    The functions of biomacromolecules are largely governed by their stereostructure (i.e., configuration and conformation). Therefore, detailed understanding of their structural properties should help in regulating the functions of artificial macromolecules. However, studying the stereostructure of a molecule in the solution state is typically difficult due to the lack of suitable analytical techniques. Vibrational circular dichroism (VCD) spectroscopy, which measures circular dichroism in the infrared region, exhibits high sensitivity toward molecular stereostructures. In this paper, we first discuss a method for the elucidation of the stereostructures of small to large molecules based on theoretical calculations of VCD. The rest of the paper is dedicated to the applications of a VCD exciton chirality method, a novel approach recently developed by the authors to interpret VCD data by observing a VCD couplet in the C=O stretching region, to various biomolecules such as peptides, carbohydrates, polyesters and lipids.
  • Shoma Mizutani, Kenta Komori, Tohru Taniguchi, Kenji Monde, Kouji Kuramochi, Kazunori Tsubaki
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 55 (33) 9553 - 9556 1433-7851 2016/08 [Refereed][Not invited]
     
    A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an alpha-bromo-beta-ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an a, beta-epoxy-gamma-lactam. Furthermore, the absolute configuration of naturally occurring (+)-rubrobramide was determined by vibrational circular dichroism. (+/-)-Flavipucine and (+/-)-isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected a-bromo-b-ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (+/-)-flavipucine, which was converted into (+/-)-isoflavipucine by thermal isomerization.
  • Tohru Taniguchi, Mai Asahata, Akihito Nasu, Yukatsu Shichibu, Katsuaki Konishi, Kenji Monde
    CHIRALITY 28 (7) 534 - 539 0899-0042 2016/07 [Refereed][Not invited]
     
    Separation of the diastereomers of glycosyl sulfoxides differing in the sulfur chirality has been difficult. This article presents a fast and scalable method for their diastereoseparation using a chiral stationary phase. The usefulness of this method was demonstrated in a 500-mg scale separation within 20 min, and in the separation of trisaccharyl sulfoxide diastereomers. (C) 2016 Wiley Periodicals, Inc.
  • Attila Mandi, Mahadeva M. M. Swamy, Tohru Taniguchi, Masaki Anetai, Kenji Monde
    CHIRALITY 28 (6) 453 - 459 0899-0042 2016/06 [Refereed][Not invited]
     
    Circular dichroism (CD) calculations of flexible natural products have been difficult because of the large number of low-energy conformers and ambiguous Boltzmann distributions. In this article, through electronic (ECD) and vibrational (VCD) studies on a natural product, (+)-daurichromenic acid, we demonstrate that derivatization of a flexible molecule can dramatically reduce its flexibility. This work also shows the usefulness of derivatization for diminishing computational expenses required for optimization and CD calculations, and for increasing the reliability of the assignment of absolute configuration. Chirality 28:453-459, 2016. (c) 2016 Wiley Periodicals, Inc.
  • Atsufumi Nakahashi, Ananda Kumar C. Siddegowda, Mostafa A. S. Hammam, Siddabasave Gowda B. Gowda, Yuta Murai, Kenji Monde
    ORGANIC LETTERS 18 (10) 2327 - 2330 1523-7060 2016/05 [Refereed][Not invited]
     
    Vibrational circular dichroism (VCD) was first applied to the stereochemical analysis of sphingosine. VCD patterns derived from the C=C stretch as well as other mid-infrared (IR) regions were practical markers to discriminate all the stereoisomers of intact sphingosine. Glutaraldehyde was found as an excellent derivatizing reagent for sphingosine which improves its solubility in VCD-friendly nonpolar solvents such as chloroform and enhances the VCD intensities by forming a rigid cyclized structure.
  • Yuta Murai, Takuma Yoshida, Lei Wang, Katsuyoshi Masuda, Yasuyuki Hashidoko, Kenji Monde, Yasumaru Hatanaka, Makoto Hashimoto
    SYNLETT 27 (6) 946 - 950 0936-5214 2016/04 [Refereed][Not invited]
     
    5-Nitro-2-propoxyaniline is one of the strongest artificial sweeteners. However, little is known about the detailed relationship of the structure and biological activity between 5-nitro-2-propoxyaniline and its sweet receptor. Photoaffinity labeling is a useful method for revealing interactions of a small bioactive compound with molecules. Therefore, we synthesized photoreactive 2-propoxyaniline derivatives as useful tools for revealing the interactions by photoaffinity labeling.
  • Yu-ki Tahara, Shuhei Obinata, Kyalo Stephen Kanyiva, Takanori Shibata, Attila Mandi, Tohru Taniguchi, Kenji Monde
    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2016 (7) 1405 - 1413 1434-193X 2016/03 [Refereed][Not invited]
     
    The enantioselective synthesis of aminoindan carboxylic acid (Aic) derivatives was achieved by Rh-catalyzed intramolecular [2+2+2] cycloaddition of amino-acid-tethered triynes. This reaction, along with recrystallization, gave chiral tethered Aic derivatives with excellent enantiomeric excess. Subsequent hydrolysis of the tethered Aic compounds afforded chiral Aic derivatives, which were further transformed into a free Aic and its dimethyl ester in good yields.
  • Mikako Kato, Mostafa A. S. Hammam, Tohru Taniguchi, Yoshiko Suga, Kenji Monde
    ORGANIC LETTERS 18 (4) 768 - 771 1523-7060 2016/02 [Refereed][Not invited]
     
    D609 (1) has been, used as a lipid-related enzyme inhibitor during the past three decades. Although it has eight possible stereoisomers, no systematic research considering its chirality has been performed,. In this paper, eight possible chiral alcohols as direct precursors of D609 were synthesized, and their stereochemistries were elucidated by a vibrational circular dichroism (VCD) technique. Phosphatidylcholine-specific phospholipase C and sphingomyelin synthase inhibition assays of these isomers showed considerable differences in their activities.
  • Mahadeva M. M. Swamy, Attila Mandi, Masaki Anetai, Kenji Monde
    NATURAL PRODUCT COMMUNICATIONS 11 (2) 193 - 195 1934-578X 2016/02 [Refereed][Not invited]
     
    A rhododaurichromanic acid A derivative was synthesized from the naturally occurring daurichromenic acid in enantiomeric pure form. Its absolute configuration was elucidated by applying VCD, ECD and DFT calculations.
  • Siddabasave B. Gowda Gowda, Seigo Usuki, Mostafa A. S. Hammam, Yuta Murai, Yasuyuki Igarashi, Kenji Monde
    JOURNAL OF LIPID RESEARCH 57 (2) 325 - 331 0022-2275 2016/02 [Refereed][Not invited]
     
    Sphingoid base derivatives have attracted increasing attention as promising chemotherapeutic candidates against lifestyle diseases such as diabetes and cancer. Natural sphingoid bases can be a potential resource instead of those derived by time-consuming total organic synthesis. In particular, glucosylceramides (GlcCers) in food plants are enriched sources of sphingoid bases, differing from those of animals. Several chemical methodologies to transform GlcCers to sphingoid bases have already investigated; however, these conventional methods using acid or alkaline hydrolysis are not efficient due to poor reaction yield, producing complex by-products and resulting in separation problems. In this study, an extremely efficient and practical chemoenzymatic transformation method has been developed using microwave-enhanced butanolysis of GlcCers and a large amount of readily available almond beta-glucosidase for its deglycosylation reaction of lysoGlcCers. The method is superior to conventional acid/base hydrolysis methods in its rapidity and its reaction cleanness (no isomerization, no rearrangement) with excellent overall yield.
  • 門出 健次, 谷口 透
    分光研究 日本分光学会 65 (2) 137 - 144 0038-7002 2016 [Not refereed][Not invited]
  • Siyuan Wang, Tohru Taniguchi, Kenji Monde, Masatoshi Kawahata, Kentaro Yamaguchi, Yuko Otani, Tomohiko Ohwada
    CHEMICAL COMMUNICATIONS 52 (21) 4018 - 4021 1359-7345 2016 [Refereed][Not invited]
     
    Nitrogen-pyramidalization of amide increases electron density on nitrogen and decreases that on carbonyl oxygen. We identified hydrogen-bonding to carbonyl of nitrogen-pyramidalized bicyclic beta-proline derivatives by crystallography, and by NMR and vibrational circular dichroism (VCD) spectroscopy in solution. Such hydrogen-bonding can switch the preferred nitrogen-pyramidalization direction, as detected by VCD spectroscopy.
  • Teigo Asai, Shuntaro Morita, Tohru Taniguchi, Kenji Monde, Yoshiteru Oshima
    ORGANIC & BIOMOLECULAR CHEMISTRY 14 (2) 646 - 651 1477-0520 2016 [Refereed][Not invited]
     
    Exposure of the fungus Chaetomium cancroideum to an NAD(+)-dependent HDAC inhibitor, nicotinamide, enhanced the production of aromatic and branched aliphatic polyketides, which allowed us to isolate new secondary metabolites, chaetophenol G and cancrolides A and B. Their structures were determined using spectroscopic analyses, and their absolute configuration was elucidated by electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and chemical transformations. Biosynthesis of the branched aliphatic polyketide skeletons in cancrolides A and B was evidenced by conducting a feeding experiment using compounds labeled with a C-13 stable isotope.
  • Tohru Taniguchi, Daisuke Manai, Masataka Shibata, Yutaka Itabashi, Kenji Monde
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 137 (38) 12191 - 12194 0002-7863 2015/09 [Refereed][Not invited]
     
    The stereochemistry of glycerophospholipids (GPLs) has been of interest for its roles in the evolution of life and in their biological activity. However, because of their structural complexity, no convenient method to determine their configuration has been reported. In this work, through the first systematic application of vibrational circular dichroism (VCD) spectroscopy to various diacylated GPLs, we have revealed that their chirality can be assigned by the sign of a VCD exciton couplet generated by the interaction of two carbonyl groups. This paper also presents spectroscopic evidence for the stereochemistry of GPLs isolated from bacteria, eukaryotes, and mitochondria.
  • Ying Ye, Atsushi Minami, Attila Mandi, Chengwei Liu, Tohru Taniguchi, Tomohisa Kuzuyama, Kenji Monde, Katsuya Gomi, Hideaki Oikawa
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 137 (36) 11846 - 11853 0002-7863 2015/09 [Refereed][Not invited]
     
    Genome mining is a promising method to discover novel secondary metabolites in the postgenomic era. We applied the Aspergillus oryzae heterologous expression system to functionally characterize cryptic bifunctional terpene synthase genes found in fungal genomes and identified the sesterfisherol synthase gene (NfSS) from Neosartorya fischeri. Sesterfisherol contains a characteristic 5-6-8-5 tetracyclic ring system and is modified by cytochrome P450 monooxygenase (NfP450) to sesterfisheric acid. The cyclization mechanism was proposed on the basis of the analysis of in vivo and in vitro enzymatic reactions with isotopically labeled precursors. The mechanism involves Cl cation-olefin IV-olefin V cyclization followed by five hydride shifts, allowing us to propose a unified biogenesis for sesterterpenes branching from bicyclic (5-15), tricyclic (5-12-5), and tetracyclic (5-6-8-5) cation intermediates. Furthermore, the mechanism is distinct from that of a separate class of di/sesterterpenes including fusicoccins and ophiobolins. The difference between mechanisms is consistent with phylogenetic analysis of bifunctional terpene synthases, suggesting that the amino acid sequence reflects the initial cyclization mode, which is most likely related to the initial conformation of a linear prenyl diphosphate.
  • Yujiro Hayashi, Tatsuya Yamazaki, Yuki Nakanishi, Tsuyoshi Ono, Tohru Taniguchi, Kenji Monde, Tadafumi Uchimaru
    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 2015 (26) 5747 - 5754 1434-193X 2015/09 [Refereed][Not invited]
     
    The diphenylprolinol silyl ether mediated asymmetric nitrocyclopropanation of -substituted ,-unsaturated aldehydes with bromonitromethane, followed by base-promoted isomerization was found to afford trans-nitrocyclopropanecarbaldehydes with all-carbon quaternary stereogenic centers with excellent diastereo- and enantioselectivities. DFT calculations indicated that the s-trans conformer of the iminium ion intermediate is more stable than the s-cis conformer. In addition, nucleophilic attack of the bromonitromethane anion to the iminium ion intermediate was calculated to occur preferentially from the opposite side of the bulky substituents of the pyrrolidine iminium intermediate.
  • Yoshihiro Yaguchi, Atsufumi Nakahashi, Nobuaki Miura, Tohru Taniguchi, Daisuke Sugimoto, Makoto Emura, Kyoko Zaizen, Yumi Kusano, Kenji Monde
    IMPORTANCE OF CHIRALITY TO FLAVOR COMPOUNDS 1212 35 - 56 0097-6156 2015 [Refereed][Not invited]
     
    Several flavor compounds have chiral centers in their structures, and it has been shown that there are differences in odor characteristics and odor thresholds between enantiomers. Vibrational CD (VCD) is a recently developed technique for the determination of the absolute stereochemistry of organic compounds assisted by ab initio quantum theoretical calculations. In this study, the VCD technique was at first applied to patchoulol, a rigid and fused tricyclic sesquiterpene alcohol. The absolute stereochemistry proposed from the observed and calculated VCD data was in agreement with the configuration reported for patchoulol. Moreover, this method was extended to odor-active flavorous furanones having a unique keto-enol tautomeric structure that is prone to racemization. The absolute stereochemistry of flavorous 2- or 5-substituted furanones such as 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF, furaneol), 2,5-dimethyl-4-methoxy-3(2H)-furanone (DMMF, mesifuran), 4-acetoxy-2,5-dimethyl-3(2H)-furanone (ADMF, furaneol acetate), 4,5-dimethyl-3-hydroxy-2(5H)-furanone (sotolon), and 5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone (maple furanone) was investigated. The examples show that the VCD technique is a very powerful tool for the determination of the absolute stereochemistry of flavor compounds.
  • Poonam Khandelwal, Pahup Singh, Tohru Taniguchi, Kenji Monde, Kohei Johmoto, Hidehiro Uekusa, Hironori Masubuti, Yoshinori Fujimoto
    PHYTOCHEMISTRY LETTERS 10 224 - 229 1874-3900 2014/12 [Refereed][Not invited]
     
    Rare derivatives of dehydroiso-alpha-lapachone, 3-hydroxydehydroiso-alpha-lapachone (1) and 3,8-dihydrox-ydehydroiso- alpha-lapachone (2) along with 5-hydroxydehydroiso-alpha-lapachone, 5-methoxy-dehydroisoa-alpha-lapachone, and 8-methoxy-dehydroiso-alpha-lapachone were isolated from a chloroform extract of the heartwood of Heterophragma adenophyllum (Bignoniaceae). A reinvestigation of the structures of 1 and 2 using NMR spectroscopic analysis and Mosher's method, combined with a vibrational circular dichroism (VCD) method and X-ray analysis for 1, indicated that the cis-orientation of the isopropenyl and OH groups originally assigned for 1 and 2 needs to be revised to the trans-orientation. Furthermore, the previously assigned R configuration at C-3 of 1 and 2 must be corrected as the S configuration. (C) 2014 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
  • Aneta Salayova, Zuzana Kudlickova, Matej Balaz, Mariana Budovska, Martina Pilatova, Jan Mojzis, Kenji Monde, Jan Petrovaj, Tatana Gondova
    TETRAHEDRON-ASYMMETRY 25 (16-17) 1221 - 1233 0957-4166 2014/09 [Refereed][Not invited]
     
    The stereoselective synthesis of the spiroindoline phytoalexin (R)-(+)-1-methoxyspirobrassinin and its unnatural (S)-(-)-enantiomer were achieved by the bromine-induced spirocyclization of 1-methoxybrassinin using chiral auxiliaries (+)- and (-)-menthol, followed by oxidation of the obtained menthyl ethers. The TFA-catalyzed methanolysis of chiral 1-methoxyspirobrassinol menthyl ethers provided (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether and its other three unnatural stereoisomers. The enantiomers of the 2-amino analogues of the indole phytoalexin (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether were prepared by the TFA-catalyzed replacement of the chiral alkoxy group with an amine. The synthesized compounds were tested in vitro on cancer cell lines and examined with enantiopure 2-amino analogues of the indole phytoalexin (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether, which showed in most cases, lower activity than the corresponding racemates. (C) 2014 Elsevier Ltd. All rights reserved.
  • Takahiro Hongen, Tohru Taniguchi, Shintaro Nomura, Jun-ichi Kadokawa, Kenji Monde
    MACROMOLECULES 47 (15) 5313 - 5319 0024-9297 2014/08 [Refereed][Not invited]
     
    Polyesters are biodegradable analogues of polypeptides, but their biochemical applications have been hampered by the lack of a method to analyze polyester conformation in a solution state. We have demonstrated that vibrational circular dichroism (VCD) spectroscopy can conveniently and accurately elucidate the conformation of polyesters through the studies on poly(L-lactic acid) (PLLA), PLLA-amylose complex, and oligo(L-lactic acid). The analysis of VCD exciton couplet of these molecules has clarified the stable left-handed helical structure of PLLA, while density functional theory calculations of oligo(L-lactic acid) have revealed its detailed structural nature.
  • Takuro Shibuta, Shigeki Sato, Masatoshi Shibuya, Naoki Kanoh, Tohru Taniguchi, Kenji Monde, Yoshiharu Iwabuchi
    HETEROCYCLES 89 (3) 631 - 639 0385-5414 2014/03 [Refereed][Not invited]
     
    The development of efficient and enantioselective intramolecular aza-spiroannulation onto benzofurans using chiral rhodium catalysis is described. The optimized reaction conditions [Rh-2(S-TCPTAD)(4) (3 mol %), PhIO (1.6 equiv), MeOH (10 equiv) in PhCF3, 0 degrees C] brought about oxidative aza-spiroannulation of 3-(carbamoylmethyl)benzofuran (3) resulting in (2R,3S)-2-methoxy-2H-spiro-[benzofuran-3,4'-oxazolidin]-2'-one (15a) in 69% yield with 86% ee, the absolute structure of which was determined by a combination of X-ray crystallography and vibrational circular dichroism (VCD) spectroscopy. The reaction is applicable to the asymmetric construction of various 2,3-dihydrobenzofuran derivatives bearing a nitrogen-containing tetrasubstituted carbon stereocenter at C3 (up to 92% ee).
  • Kenta Komori, Tohru Taniguchi, Shoma Mizutani, Kenji Monde, Kouji Kuramochi, Kazunori Tsubaki
    ORGANIC LETTERS 16 (5) 1386 - 1389 1523-7060 2014/03 [Refereed][Not invited]
     
    The first synthesis of (+/-)-berkeleyarnide D has been accomplished. The key features of this synthesis include the formation of an alpha,beta-epoxy-gamma-lactam via a Darzens reaction and the construction of a spirocyclic ring system by a C-acylation reaction followed by an intramolecular spirocyclization via an epoxide-opening reaction. Following optical resolution by chiral HPLC, the absolute configurations of both enantiomers of berkeleyamide D were determined by the vibrational circular dichroism exciton chirality method.
  • Teigo Asai, Tohru Taniguchi, Takashi Yamamoto, Kenji Monde, Yoshiteru Oshima
    ORGANIC LETTERS 15 (17) 4320 - 4323 1523-7060 2013/09 [Refereed][Not invited]
     
    Spiroindicumides A (1) and B (2), novel spirolactone polyketides, were isolated from a filamentous fungus, Chaetomium indicum, cultivated in the presence of a histone deacetylase inhibitor. Their structures including relative configurations were determined by spectroscopic analyses. Their absolute configurations were unambiguously assigned by the vibrational circular dichroism (VCD) exciton chirality method using only ca. 0.3 mg of each sample. This study presents the first application of the VCD exciton approach to novel natural products. A possible biosynthetic pathway of the new compounds was also proposed.
  • Teigo Asai, Takashi Yamamoto, Naoki Shirata, Tohru Taniguchi, Kenji Monde, Isao Fujii, Katsuya Gomi, Yoshiteru Oshima
    ORGANIC LETTERS 15 (13) 3346 - 3349 1523-7060 2013/07 [Refereed][Not invited]
     
    Epigenetic manipulation of gene expression in Chaetomium indicum using a HDAC inhibitor led to the isolation of structurally diverse chaetophenols, and 3, 4 and 5 bear unprecedented polycyclic skeletons. The expression of two silent genes (pksCH-1 and pksCH-2) for nonreducing PKSs involved in chaetophenol biosynthesis was associated with an increase of histone acetylation level. The heterologous gene expression study in Aspergillus oryzae revealed pksCH-2 to be the NR-PKS gene for 8.
  • Teigo Asai, Sae Otsuki, Tohru Taniguchi, Kenji Monde, Kouwa Yamashita, Hiroaki Sakurai, Tomoji Ozeki, Yoshiteru Oshima
    TETRAHEDRON LETTERS 54 (26) 3402 - 3405 0040-4039 2013/06 [Refereed][Not invited]
     
    Mycosphines A-D (1-4), comprising a class of new short-branched fatty acid dimers, were found in the cultures of an endophytic fungus, Mycosphaerella sp., isolated from Aloe arborescens. The structures, including the absolute stereochemistries were determined by spectroscopic analysis, single crystal Xray diffraction, and vibrational circular dichroism (VCD). (C) 2013 Elsevier Ltd. All rights reserved.
  • 糸状菌二次代謝を活性化するNAD依存型HDAC阻害剤の探索とそれを用いた新規天然物の創出
    森田 峻太郎, 浅井 禎吾, 谷口 透, 門出 健次, 櫻井 博章, 尾関 智二, 山下 幸和, 大島 吉輝
    日本薬学会年会要旨集 (公社)日本薬学会 133年会 (2) 177 - 177 0918-9823 2013/03 [Refereed][Not invited]
  • Teigo Asai, Shuntaro Morita, Naoki Shirata, Tohru Taniguchi, Kenji Monde, Hiroaki Sakurai, Tomoji Ozeki, Yoshiteru Oshima
    ORGANIC LETTERS 14 (21) 5456 - 5459 1523-7060 2012/11 [Refereed][Not invited]
     
    Cultivation of Chaetomium mollipilium with nicotinamide, a NAD(+)-dependent HDAC inhibitor, stimulated its secondary metabolism, leading to the isolation of structurally diverse new C-13-polyketides, mollipilin A-E (1-5) as well as two known compounds (6 and 7). Spectroscopic methods, X-ray single crystal diffraction analysis, and VCD elucidated the absolute configurations of structures 1-6, and plausible biosynthetic pathways for 1-7 were proposed based on structural relationships. Mollipilins A (1) and B (2) exhibited moderate growth inhibitory effects on HCT-116 cells.
  • Teigo Asai, Dan Luo, Yutaro Obara, Tohru Taniguchi, Kenji Monde, Kouwa Yamashita, Yoshiteru Oshima
    TETRAHEDRON LETTERS 53 (17) 2239 - 2243 0040-4039 2012/04 [Refereed][Not invited]
     
    The secondary metabolite production of Cordyceps annullata, an entomopathogenic fungus, was clearly enhanced by the addition of suberoyl bis-hydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, to the culture medium. Four new 2,3-dihydrobenzofurans, annullatins A-D (1-4), and a new aromatic polyketide, annullatin E (5) were isolated from the culture medium, and the structures, including the absolute stereochemistries, were determined by spectroscopic analysis, vibrational circular dichroism (VCD), and chemical transformations. Annullatin A (1) exhibited potent agonistic activity toward the cannabinoid receptors CB1 and CB2. Annullatin B (2) and D (4) displayed CB1 agonistic activity and CB2 inverse agonistic activity. (c) 2012 Elsevier Ltd. All rights reserved.
  • Takanori Shibata, Mayu Miyoshi, Toshifumi Uchiyama, Kohei Endo, Nobuaki Miura, Kenji Monde
    TETRAHEDRON 68 (12) 2679 - 2686 0040-4020 2012/03 [Refereed][Not invited]
     
    An enantioselective intramolecular [2+2+2] cycloaddition of 2-aminophenol-tethered triynes and diyne-nitriles proceeded using the chiral Rh catalysts, and tripodal cyclophanes and pyridinophanes with a long ansa chain (up to [16]pyridinophane) were obtained in acceptable yield with high to almost perfect ee. In the reaction of triynes, we elucidated that the oxygen atom at the alkyne terminus is essential for the excellent enantioselectivity. For the construction of cage-type molecule, the choice of rigid tether, which connects 1,6-diyne moiety with a side carbon chain having alkyne or cyano group on its terminus, was important, and 8-amino-2-naphthol moiety was also a preferable tether. (C) 2012 Elsevier Ltd. All rights reserved.
  • Tohru Taniguchi, Kenji Monde
    Comprehensive Chiroptical Spectroscopy 2 795 - 818 2012/02/17 [Refereed][Not invited]
  • Tohru Taniguchi, Kenji Monde
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 134 (8) 3695 - 3698 0002-7863 2012/02 [Refereed][Not invited]
     
    The interaction of two IR chromophores yields a strong vibrational circular dichroism couplet whose sign reflects the absolute configuration of the molecule. We present a method to determine absolute configuration of a chiral molecule based on this couplet without need of theoretical calculation. Not only can this method analyze various molecules whose absolute configuration is difficult to determine by other spectroscopic methods, but also it can significantly enhance VCD signals.
  • Yutaka Aoyagi, Akira Yamazaki, Reiko Kato, Fukuya Tobe, Haruhiko Fukaya, Tadateru Nishikawa, Atsufumi Nakahashi, Nobuaki Miura, Kenji Monde, Koichi Takeya
    TETRAHEDRON LETTERS 52 (16) 1851 - 1853 0040-4039 2011/04 [Refereed][Not invited]
     
    Salvileucalin C (1), a novel neoclerodane diterpene having an unprecedented carbon framework and a structurally closely related salvileucalin D (2) were isolated and their absolute structures were elucidated by the vibrational circular dichroism (VCD) spectra. (C) 2011 Elsevier Ltd. All rights reserved.
  • Atsufumi Nakahashi, Yoshihiro Yaguchi, Nobuaki Miura, Makoto Emura, Kenji Monde
    JOURNAL OF NATURAL PRODUCTS 74 (4) 707 - 711 0163-3864 2011/04 [Refereed][Not invited]
     
    Sotolon (1) and Maple furanone (2) are naturally occurring chiral furanones. These 5-substituted-2(5H)-furanones are industrially significant aroma compounds due to their characteristic organoleptic properties, and extraordinarily low odor thresholds. Each enantiomer of 1 and 2 was successfully obtained by preparative enantioselective supercritical fluid chromatography. The absolute configuration of 1 was confirmed as (R)-(-)-1 and (S)-(+)-1 by:adopting the vibrational circular dichroism (VCD) approach. The absolute configuration of 2, which has remained ambiguous since its discovery in 1957, was determined as,(R)-(+)-2 and (S)-(-)-2 for the first tune by the VCD technique. Surprisingly, the signs of the optical rotation of 2;are opposite. of those of 1 regardless of their identical absolute configurations This observation emphasizes the risk in, absolute configurational assignments based on comparison of optical rotation signs of similar structures Odor evaluation of the enantiomers of 2 revealed different odor intensities
  • Takuma Fujita, Kazuhiro Obata, Shunsuke Kuwahara, Atsufumi Nakahashi, Kenji Monde, John Decatur, Nobuyuki Harada
    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 33 (33) 6372 - 6384 1434-193X 2010/11 [Refereed][Not invited]
     
    Enantiopure (R)-(+)-[VCD(-)984]-4-ethyl-4-methyloctane (1), a cryptochiral hydrocarbon with a quaternary chiral center, was synthesized by the use of 2-methoxy-2-(1-naphthyl)propionate (M alpha NP) and (-)-camphorsultam dichlorophthalic (CSDP) acid methods. The diastereomeric M alpha NP and CSDP acid esters prepared from racemic 2-butyl-2-methyl-1-tetralols, were effectively separated by HPLC on silica gel, and their absolute configurations were unambiguously determined by X-ray crystallographic analysis and H-1 NMR anisotropy methods. The recovered enantiopure 2-butyl-2methyl-1-tetralol [(1S,2S)-(+)-cis-9] was then converted into the hydrocarbon (+)-1, the R absolute configuration of which was unambiguously determined for the first time. The structure of hydrocarbon 1 was also confirmed by NMR HSQC-TOCSY analysis.
  • Shunsuke Kuwahara, Kazuhiro Obata, Takuma Fujita, Nobuaki Miura, Atsufumi Nakahashi, Kenji Monde, Nobuyuki Harada
    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY 33 (33) 6385 - 6392 1434-193X 2010/11 [Refereed][Not invited]
     
    To characterize precisely the chiroptical properties of 4-ethyl-4-methyloctane (1), one of the so-called cryptochiral compounds, the enantiomer (S)-(-)-[VCD(+)984]-1 was synthesized in an enantiopure form. The observed specific rotation values at 365 nm of both enantiomers agreed well, but were opposite in sign, confirming their enantiomeric relationship, although their absolute values were very small, reflecting their cryptochirality. The vibrational circular dichroism (VCD) spectra of both enantiomers were measured neat and showed characteristic Cotton effects around 1150-900 cm(-1); the VCD spectral curves were mirror images of each other. Based on the observed positive VCD band at 984 cm(-1) for (S)-(-)-1, its absolute configuration was fully designated as (S)-(-)-[VCD(+)984]-1. The VCD spectrum was quantum chemically calculated by the DFT MO method at the B3PW91/6-31G(d,p) level, and the simulated VCD curve for (S)-1 agreed very well with the observed VCD spectrum of (S)-(-)-1, confirming the absolute configuration.
  • Kaori Chiba, Kazutomo Kurogi, Kenji Monde, Mai Hashimoto, Masafumi Yoshida, Hiroyuki Mayama, Kaoru Tsujii
    COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS 354 (1-3) 234 - 239 0927-7757 2010/02 [Not refereed][Not invited]
     
    Super water- and highly oil-repellent films have been synthesized by electrochemical polymerization of some new monomers of fluorinated alkylpyrroles. The surface roughness of the films was controlled by the polymerization conditions such as concentration of monomers, applied voltages, polymerization time and so on. The contact angles on the most liquid-repellent film surfaces are about 160 degrees and 140 degrees for water and salad oil, respectively. The sliding angle for the salad oil is 9.5 +/- 2.5 degrees which is much better than that on the poly(alkylpyrrole) films coated with a fluorinated aikylsilane coupling agent. Thermal and organic solvent stability for the liquid-repellent property of the films were quite good to be used practically. (C) 2009 Elsevier B.V. All rights reserved.
  • Makoto Emura, Yoshihiro Yaguchi, Atsufumi Nakahashi, Daisuke Sugimoto, Nobuaki Miura, Kenji Monde
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 57 (21) 9909 - 9915 0021-8561 2009/11 [Refereed][Not invited]
     
    Chiral naturally occurring aroma compounds often exhibit enantiomeric excesses due to their stereoselective biogenesis. In general, significant organoleptic differences are perceived between these enantiomers. Chiral 2-substituted-3(2H)-furanones, featuring a unique keto-enol tautomer, the cause of their racemization, have been known to play an important role in flavor because of their extremely low threshold values and their burnt sugar odor characteristics. Since the discovery of these important aroma chemicals, they have been used in large quantities as raw materials in the flavor and fragrance industry. However, absolute configurations of these furanone derivatives have remained ambiguous for the past 40 years. Here optical resolutions of 2,5-dimethyl-4-hydroxy-3(2H)-furanone 2,5-dimethyl-4-methoxy-3(2H)-furanone, and 4-acetoxy-2,5-dimethyl-3(2H)-furanone were accomplished using chiral CO(2) supercritical fluid chromatography (SFC). Their absolute configurations were unraveled for the first time using the vibrational circular dichroism (VCD) technique as well as by chemical relay reactions. Odor evaluation of each enantiomer revealed relationships between their configurations and odor activities.
  • Atsufumi Nakahashi, Nobuaki Miura, Kenji Monde, Sachiko Tsukamoto
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 19 (11) 3027 - 3030 0960-894X 2009/06 [Not refereed][Not invited]
     
    Hexylitaconic acid (1) is an intriguing natural product possessing a chiral carbon, and both its enantiomers have been found in nature. Enantiomeric pure (+)-(1) and (-)-(1) were successfully prepared by racemic synthesis followed by enantiomeric separation in a chiral HPLC system. Their absolute configurations were clarified by the vibrational circular dichroism technique using their methyl esters 2 and lactones 3. Their inhibitory activities against the interaction of p53-HDM2 were also examined. (C) 2009 Elsevier Ltd. All rights reserved.
  • De Lie An, Qiang Chen, Jingkun Fang, Hong Yan, Akihiro Orita, Nobuaki Miura, Atsufumi Nakahashi, Kenji Monde, Junzo Otera
    TETRAHEDRON LETTERS 50 (15) 1689 - 1692 0040-4039 2009/04 [Refereed][Not invited]
     
    Stereochemical study of cyclophynes, which is otherwise rather difficult to perform, can be achieved by vibrational CD spectroscopy. (C) 2009 Published by Elsevier Ltd.
  • Tohru Taniguchi, Connor L. Martin, Kenji Monde, Koji Nakanishi, Nina Berova, Larry E. Overman
    JOURNAL OF NATURAL PRODUCTS 72 (3) 430 - 432 0163-3864 2009/03 [Refereed][Not invited]
     
    The absolute configuration of actinophyllic acid (-)-1, an alkaloid with an unprecedented 2,3,6,7,9,13c-hexahydro-1H-1,7,8-(methanetriyloxymethano)pyrrolo[1',2':1,2]azacino[4,3-b]indole-8(5H)-carboxylic acid skeleton isolated from Alstonia actinophylla, was determined through the study of its corresponding methyl ester 2. Racemic 2 was separated into (+)-2 and (-)-2 enantiomers, and they were assigned unambiguously as 15S,16R,19R,20R,21S and 15R,16S,19S,20S,21R, respectively, by the use of optical rotation and electronic circular dichroism. Finally, (-)-2 was characterized as the methyl ester of naturally occurring (-)-1. The assigned 15R,16S,19S,20S,21R-configuration of (-)-1 is consistent with a proposed biosynthetic pathway.
  • Kenji Monde, Atsufumi Nakahashi, Nobuaki Miura, Yoshihiro Yaguchi, Daisuke Sugimoto, Makoto Emura
    CHIRALITY 21 (1E) E110 - E115 0899-0042 2009 [Not refereed][Not invited]
     
    A mixture of tautomers with unique keto-enol structures, 5-ethyl-4-hydroxy-2-methylfuran-3(2H)-one and 2-ethyl-4-hydroxy-5-methylfuran-3(2H)-one (EHMF, homofuraneol, 1a and 1b), comprises four structural isomers including their enantiomers. The four isomers were successfully separated by chromatographic optical resolution, and their odor evaluation was performed. Determination of the absolute chemistry of 1a and 1b were accomplished for the first time by direct measurement of the VCD spectra of their methyl ether derivatives 4a and 4b compared with the calculated ones as well as chemical relay reaction. The relationship between odor characteristics and stereochemistry was also examined. Chirality 21:E110-E115, 2009. (C) 2009 Wiley-Liss, Inc.
  • Hiroaki Nakagawa, Miki Ohira, Shunji Hayashi, Shigeaki Abe, Shin Saito, Noriko Nagahori, Kenji Monde, Yasuro Shinohara, Naoki Fujitani, Hirosato Kondo, Shin-Ichi Akiyama, Akira Nakagawara, Shin-Ichiro Nishimura
    CANCER LETTERS 270 (2) 295 - 301 0304-3835 2008/11 [Not refereed][Not invited]
     
    Cisplatin, cis-diamineplatinum-(II) dichloride (CDDP), is one of the most common and valuable chemotherapeutic reagents for various cancers. However, it is well known that tumor cells gain acquired or intrinsic resistance to treatment by this anti-cancer reagent. In spite of extensive efforts using genetic and proteomic approaches, the mechanism underlying CDDP resistance remains unclear. In the present study, we report drastic structural changes in the N-glycans of glycoproteins in CDDP-resistant tumor cells (the KCP-4 cell line obtained from KB-3-1 human carcinoma cells). It was suggested that the CDDP-resistant cells exhibited an increase in one of the high-mannose-type glycans, particularly M8.1. This N-glycan is well known as a tag for the transport of unfolded protein from the endoplasmic reticulum to the lysosome, a process known as endoplasmic reticulum-associated degradation (ERAD) system. The revertant cells (KCP-4R) obtained from the KCP-4 cell line showed almost the same glycoform profile as that of the parental cells, suggesting that N-glycan biosynthesis in tumor cells clearly corresponds to the alteration in the sensitivity against CDDP. Gene expression analysis using a cDNA microarray showed a decrease in the expression of major histocompatibility complex (MHC) proteins in the resistant cells. MHC proteins form a complex with lysosome-degradated proteins and are presented on the cell surface. These results suggest that CDDP tolerance in KCP-4 cells is caused by a defect in the ERAD system. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
  • Yoshihiro Yaguchi, Atsufumi Nakahashi, Nobuaki Miura, Daisuke Sugimoto, Kenji Monde, Makoto Emura
    ORGANIC LETTERS 10 (21) 4883 - 4885 1523-7060 2008/11 [Not refereed][Not invited]
     
    2-Substituted-3(2H)-furanone derivatives are industrially significant aroma compounds possessing a unique keto-enol tautomeric feature causing their racemization. Absolute configurations of two flavorous furanones, which have remained unclear for the past 40 years since their discovery, were clarified by the vibrational circular dichroism technique as well as chemical relay reactions. Odor evaluation of each enantiomer revealed relationships between their configurations and their odor activities.
  • Tohru Taniguchi, Ikuko Tone, Kenji Monde
    CHIRALITY 20 (3-4) 446 - 453 0899-0042 2008/03 [Not refereed][Not invited]
     
    Application of vibrational circular dichroism (VCD) spectroscopy to structural analysis of carbohydrates has recently progressed. However, few studies on glycoconjugates VCD have thus far been reported, despite the fact that naturally occurring carbohydrates exist as various glycoconjugates. To further explore the application of the VCD technique, we have measured a series of aromatic glycosides and found that axial aromatic glycosides exhibited a negative band at around 1230 cm(-1) while equatorial ones showed flat features in this region. This is the first structure-spectra relationship on glycoconjugate VCD that distinguishes the stereochemistry of the sugar anomers. Several model compounds were prepared and their vibrational properties calculated by using the density functional theory (DFT) method, which assigned the vibrational mode of this band based on the stretching motion of the glycosidic oxygen and aromatic carbon. This concept that aglycan parts can reflect stereochemical information of sugar moieties may encourage further VCD studies on glycoconjugates to realize practical structural analysis of carbohydrates.
  • Taku Nakahara, Ryo Hashimoto, Hiroaki Nakagawa, Kenji Monde, Nobuaki Miura, Shin-Ichiro Nishimura
    NUCLEIC ACIDS RESEARCH 36 D368 - D371 0305-1048 2008/01 [Not refereed][Not invited]
     
    Glycobiology has been brought to public attention as a frontier in the post-genomic era. Structural information about glycans has been accumulating in the Protein Data Bank (PDB) for years. It has been recognized, however, that there are many questionable glycan models in the PDB. A tool for verifying the primary structures of glycan 3D structures is evidently required, yet there have been no such publicly available tools. The Glycoconjugate Data Bank: Structures (GDB:Structures, http://www.glycostructures.jp) is an annotated glycan structure database, which also provides an N-glycan primary structure (or glycoform) verification service. All the glycan 3D structures are detected and annotated by an in-house program named 'getCARBO'. When an N-glycan is detected in a query coordinate by getCARBO, the primary structure of the glycan is compared with the most similar entry in the glycan primary structure database (KEGG GLYCAN), and unmatched substructure(s) are indicated if observed. The results of getCARBO are stored and presented in GDB: Structures.
  • Tohru Taniguchi, Kenji Monde, Koji Nakanishi, Nina Berova
    ORGANIC & BIOMOLECULAR CHEMISTRY 6 (23) 4399 - 4405 1477-0520 2008 [Not refereed][Not invited]
     
    The optical rotation, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) of chiral sulfinates have been studied experimentally, and analysed by density functional theory calculation, aiming at establishing a reliable and convenient methodology to determine their absolute configuration. Through the study on a model chiral sulfinate with known absolute configuration, (R)-(+)-methyl p-toluenesulfinate ((R)-(+)-1), each technique was found to be reliable in assigning chirality of sulfinates. We then applied these methods to a synthetically prepared cruciferous phytoalexin, brassicanal C ((-)-2), and unambiguously determined its absolute configuration as S. The advantages and disadvantages of each spectroscopy on sulfinates are also discussed.
  • Zuzana C. Curillova, Peter Kutschy, Mariana Budovska, Atsufumi Nakahashi, Kenji Monde
    TETRAHEDRON LETTERS 48 (46) 8200 - 8204 0040-4039 2007/11 [Not refereed][Not invited]
     
    Stereoselective synthesis of cruciferous indole phytoalexin (R)-(+)-1-methoxyspirobrassinin and its unnatural (S)-(-)-enantiomer was achieved by spirocyclization of 1-methoxybrassinin in the presence of (+)- and (-)-menthol and subsequent oxidation of the obtained menthyl ethers. Methanolysis of menthyl ethers in the presence of TFA afforded (2R,3R)-(-)-1-methoxyspirobrassinol methyl ether as well its unnatural (2S,3S)-, (2R,3S)-, and (2S,3R)-isomers. (C) 2007 Elsevier Ltd. All rights reserved.
  • Atsufumi Nakahashi, Tohru Taniguchi, Nobuaki Miura, Kenji Monde
    ORGANIC LETTERS 9 (23) 4741 - 4744 1523-7060 2007/11 [Not refereed][Not invited]
     
    Systematic VCD studies of N-acetylneuraminic acid (Neu5Ac), a recognition-related unique carbohydrate, were performed for the first time. Two pairs of anomeric isomers regarding a quaternary C2 asymmetric carbon of Neu5Ac derivatives were synthesized. VCD spectral patterns around the ester carbonyl region, as well as other NOR regions, would be practical markers to distinguish the C2 stereochemistry.
  • Tohru Taniguchi, Kenji Monde
    Chemistry – An Asian Journal 2 (10) 1258 - 1266 1861-4728 2007/10 [Refereed][Not invited]
     
    Preliminary reports of the nature of the vibrational circular dichroism (VCD) peak at around 1145 cm(-1), which is characteristic of axial glycosidic sugars and is called the glycoside band (J. Am. Chem. Soc. 2004, 126, 9496), have been throughly examined. Through systematic carbohydrate measurements, it was found that the sign of the glycoside band reflects not only the anomeric configuration but also the pyranose conformation. Isotope and theoretical studies characterized its vibrational mode as C1-H1 deformation coupled with C1-O1 stretching, which indicates its applicability to more-complicated glycoconjugates. In this study, for the first time, carbohydrate VCD spectra were reliably predicted by means of density functional theory (DFT) calculations. The VCD technique was applied to glycopeptides, and simultaneous analysis of both the carbohydrate and aglycan parts was carried out.
  • Hisako Sato, Tohru Taniguchi, Atsufumi Nakahashi, Kenji Monde, Akihiko Yamagishi
    INORGANIC CHEMISTRY 46 (16) 6755 - 6766 0020-1669 2007/08 [Not refereed][Not invited]
     
    Vibrational circular dichroism (VCD) spectra of a series of [M(III)(acac)(3)] (acac = acetylacetonato; M = Cr, Co, Ru, Rh, Ir, and Al) and [M(III)(acac)(2)(dbm)] (dbm = dibenzoylmethanato; M = Cr, Co, and Ru) have been investigated experimentally and/or theoretically in order to see the effect of the central metal ion on the vibrational dynamics of ligands. The optical antipodes give the mirror-imaged spectra in the region of 1700-1000 cm(-1). The remarkable effect of the central metal ion is observed experimentally on the VCD peaks due to C-O stretches (1500-1300 cm(-1)) for both [M(III)(acac)(3)] and [M(III)(acac)(2)(dbm)]. In the case of Delta-[M(III)(acac)(3)], for example, the order of frequency of two C-O stretches (E and A(2) symmetries) is dependent on the kind of a central metal ion as follows: E (-) > A(2) (+) for M = Co, Rh, and Ir, while A(2) (+) > E (-) for M = Cr and Ru. In the case of Delta-[M(III)(acac)(2)(dbm)], the order of frequency of three C-O stretches (A, B, and B symmetries) is as follows: A (-) > B (+) > B (+) for Co(III), B (+) > A (-) > B (-) for Cr(III), and A (-) > B (+) > B (-) for Ru(III). These results imply that the energy levels of C-O stretches are delicately affected by the kind of central metal ion. Since such detailed information is not obtained from the IR spectra alone, the VCD spectrum can probe the effect of the central metal ion on interligand cooperative vibration modes.
  • Hia Myoe Min, Mya Aye, Tohru Taniguchi, Nobuaki Miura, Kenji Monde, Kazuhiko Ohzawa, Toshiaki Nikai, Masatake Niwa, Yoshiaki Takaya
    TETRAHEDRON LETTERS 48 (35) 6155 - 6158 0040-4039 2007/08 [Refereed][Not invited]
     
    (+)-Alternamin (1), a new dihydrofuranocoumarin, was isolated from the aerial parts of Murraya alternans (Kurz) Swinge. The analysis 2-D NMR correlation of (+)-1 led to either of linear dihydrofuranocoumarin (2A, 2C) or angular one (213). An IR and a vibrational circular dichroism (VCD) studies were conducted to distinguish the structure and to assign the absolute configuration. By comparison of the observed spectra with the calculated spectra for (S)-2A, (S)-2B, and (R)-2C, the molecular structure of (+)-1 was determined to be (S)-(+)-5,8-dimethoxymarmesin. The compound exhibited antidote activity against snake venom from Trimeresurus flavoviridis, affording experimental support for the pharmacological use of M. alternans. (c) 2007 Elsevier Ltd. All rights reserved.
  • Shintaro Yamane, Norimasa Iwasaki, Yasuhiko Kasahara, Kazuo Harada, Tokifumi Majima, Kenji Monde, Shin-ichiro Nishimura, Akio Minami
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 81A (3) 586 - 593 1549-3296 2007/06 [Not refereed][Not invited]
     
    In this study, we successfully developed three-dimensional scaffolds fabricated from the chitosan-based hyaluronic acid hybrid polymer fibers, which can control the porous structure. To determine the adequate pore size for enhancing the chondrogenesis of cultured cells, we compared the behaviors of rabbit chondrocytes in scaffolds comprising different pore sizes (100, 200, and 400 mu m pore size). Regarding the cell proliferation, there was no significant difference among the three groups. On the other hand, glycosaminoglycan contents in the 400 pm group significantly increased during the culture period, compared with those in the other groups. The ratio of type II to type I collagen mRNA level was also significantly higher in the 400 mu m group than in the other groups. These results indicate that our scaffold with 400 mu m pore size significantly enhances the extracellular matrix synthesis by chondrocytes. Additionally, the current scaffolds showed high mechanical properties, compared with liquid and gel materials. The data derived from this study suggest great promise for the future of a novel fabricated material with relatively large pore size as a scaffold for cartilage regeneration. The biological and mechanical advantages presented here will make it possible to apply our scaffold to relatively wide cartilaginous lesions. (C) 2006 Wiley Periodicals, Inc. J Biomed Mater Res 81A: 586-593, 2007.
  • Takuma Fujita, Kazuhiro Obataa, Shunsuke Kuwahara, Nobuaki Miura, Atsufumi Nakahashi, Kenji Monde, John Decatur, Nobuyuki Harada
    TETRAHEDRON LETTERS 48 (24) 4219 - 4222 0040-4039 2007/06 [Not refereed][Not invited]
     
    Enantiopure (R)-(+)-[VCD(+)945]-4-ethyl-4-methyloctane, the simplest chiral saturated hydrocarbon with a quaternary stereogenic center, was synthesized by the use of M alpha NP acid method, and its absolute configuration was first unambiguously determined by the H-1 NMR anisotropy, X-ray crystallography, and VCD methods. (c) 2007 Elsevier Ltd. All rights reserved.
  • Taniguchi Tohru, Monde Kenji
    TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY 19 (107) 147 - 164 0915-7352 2007/05 [Refereed][Not invited]
     
    This review describes theoretical and experimental aspects of vibrational circular dichroism (VCD) spectroscopy, and its application to structure analysis of carbohydrates targeting on their chiral property.
  • Tohru Taniguchi, Kenji Monde
    ORGANIC & BIOMOLECULAR CHEMISTRY 5 (7) 1104 - 1110 1477-0520 2007 [Not refereed][Not invited]
     
    The structural features of carbohydrates are a combination of 1) sequence and types of mono-sugars, 2) stereochemistry of their glycosidic linkages, and 3) their glycosidic linkage sites. We performed the first systematic VCD study on glycoside linking site discrimination. VCD spectra, in the CH stretching region from 2000 to 4000 cm(-1), of eleven glucobioses (trehalose (alpha 1-alpha 1), neotrehalose (alpha 1-beta 1), isotrehalose (beta 1-beta 1), kojibiose (alpha 1-2), nigerose (alpha 1-3), maltose (alpha 1-4), isomaltose (alpha 1-6), sophorose (beta 1-2), laminaribiose (beta 1-3), cellobiose (beta 1-4), gentiobiose (beta 1-6)) suggested a possible new discrimination method for glyco analysis, while VCD spectra in the mid-IR region distinguished the stereochemistry (alpha or beta) of the glycosidic linkage. Both reducing and nonreducing glucobioses showed different VCD spectral features compared to their constituent D-glucose and the anomer-fixed model compounds. Interresidue interaction such as hydrogen bonding was suggested to cause these spectral differences. Interplay between residues is a common phenomenon and thus VCD analysis could be applicable to other di-, oligo- or poly-saccharides. Several isotropic labeled compounds were also measured to support spectral assignment and interpretation.
  • Kenji Monde, Nobuaki Miura, Tohru Taniguchi
    Kagaku to Seibutsu 日本農芸化学会 45 (7) 455 - 458 0453-073X 2007 [Not refereed][Not invited]
  • Tohru Taniguchi, Kenji Monde, Shin-Ichiro Nishimura, Jun Yoshida, Hisako Sato, Akihiko Yamagishi
    Molecular Crystals and Liquid Crystals 460 (1) 107 - 116 1542-1406 2006/12/01
  • MONDE Kenji
    Kobunshi The Society of Polymer Science, Japan 55 (7) 516 - 519 0454-1138 2006/07/01
  • Kenji Monde, Tohru Taniguchi, Nobuaki Miura, Charles S. Vairappan, Minoru Suzuki
    TETRAHEDRON LETTERS 47 (26) 4389 - 4392 0040-4039 2006/06 [Not refereed][Not invited]
     
    Diastercomeric mixture on the peroxide portion of ail endoperoxide acetylmajapolene A (1) was efficiently separated by HPLC on a chiral column, submitting to vibrational circular dichroism (VCD) investigation. The ab initio theoretical VCD and IR calculations of 1a and 1b were performed by density functional theory (DFT) using the B3PW91/6-31G(d.p) level of theory. Focusing on an isolated characteristic peroxide vibrational band, absolute configurations of 1a and 1b were unambiguously determined Lis (1R,4R,7S,10S) and (1S,4S,7S,10S), respectively. This is the first VCD application to endoperoxides which exist abundantly in nature. (c) 2006 Elsevier Ltd. All rights reserved.
  • K Monde, T Taniguchi, N Miura, CS Vairappan, M Suzuki
    CHIRALITY 18 (5) 335 - 339 0899-0042 2006/05 [Not refereed][Not invited]
     
    Two brominated sesquiterpenes, majapolene B (1) and acetylmajapolene B (2), isolated from the red algal genus Laurencia were investigated using vibrational circular dichroism (VCD). The ab initio theoretical VCD and IR calculations of 1 and 2 were performed by density functional theory (DFT) using the B3PW91/631G(d,p) basis set. The experimental VCD spectra and corresponding population-weighted theoretical VCD spectra were found to be in excellent agreement in CCl4 solution in the 1800-850 cm(-1) region, which allowed unambiguous determination of the absolute configurations of (-)-1 and (-)-2 as 7S,10S and 7S,10S, respectively.
  • Kenji Monde, Nobuaki Miura, Mai Hashimoto, Tohru Taniguchi, Tamotsu Inabe
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 (18) 6000 - 6001 0002-7863 2006/05 [Not refereed][Not invited]
  • Hisako Sato, Tohru Taniguchi, Kenji Monde, Shin-Ichiro Nishimura, Akihiko Yamagishi
    CHEMISTRY LETTERS 35 (4) 364 - 365 0366-7022 2006/04 [Not refereed][Not invited]
     
    The VCD spectra of a series of tris(acetylacetonato)metal(III) ([M(acac)(3)] with M = Co, Cr, Ru, and Rh) have revealed a new aspect concerning the effects of a central metal ion on the vibrational energy levels split by the inter-ligand interactions. Our present view is that the correlated vibrational motions of vicinal ligands are affected by the d-electron configuration of a central metal ion.
  • N Miura, T Taniguchi, K Monde, SI Nishimura
    CHEMICAL PHYSICS LETTERS 419 (4-6) 326 - 332 0009-2614 2006/02 [Not refereed][Not invited]
     
    A theoretical investigation of stable conformations Of D-glucopyranose was carried out using the density functional theory (DFT). Solvation effects were also evaluated with polarization continuum model (PCM) calculations. The 6-311++G(2d,2p) basis sets were appropriate. The estimated populations of gg, gt, and tg hydroxylmethyl rotamers were 53, 46, and 1 for alpha-(D)-glucopyranose and 48, 5 1, and I for beta-D-glucopyranose. Estimated ratios of alpha- to beta-anomers were 26 and 74, respectively. These populations are in good agreement with the NMR experiments. The first calculations of the vibrational circular dichroism (VCD) spectra Of D-glucopyranose were also performed. (c) 2005 Elsevier B.V. All rights reserved.
  • R Uematsu, J Furukawa, H Nakagawa, Y Shinohara, K Deguchi, K Monde, SI Nishimura
    MOLECULAR & CELLULAR PROTEOMICS 4 (12) 1977 - 1989 1535-9476 2005/12 [Not refereed][Not invited]
     
    Despite recent advances in our understanding of the significance of the protein glycosylation, the throughput of protein glycosylation analysis is still too low to be applied to the exhaustive glycoproteomic analysis. Aiming to elucidate the N-glycosylation of murine epidermis and dermis glycoproteins, here we used a novel approach for focused proteomics. A gross N-glycan profiling (glycomics) of epidermis and dermis was first elucidated both qualitatively and quantitatively upon N-glycan derivatization with novel, stable isotope-coded derivatization reagents followed by MALDI-TOF(/TOF) analysis. This analysis revealed distinct features of the N-glycosylation profile of epidermis and dermis for the first time. A high abundance of high mannose type oligosaccharides was found to be characteristic of murine epidermis glycoproteins. Based on this observation, we performed high mannose type glycoform-focused proteomics by direct tryptic digestion of protein mixtures and affinity enrichment. We identified 15 glycoproteins with 19 N-glycosylation sites that carry high mannose type glycans by off-line LC-MALDI-TOF/TOF mass spectrometry. Moreover the relative quantity of microheterogeneity of different glycoforms present at each N-glycan binding site was determined. Glycoproteins identified were often contained in lysosomes (e.g. cathepsin L and gamma-glutamyl hydrolase), lamellar granules (e.g. glucosylceramidase and cathepsin D), and desmosomes (e g. desmocollin 1, desmocollin 3, and desmoglein). Lamellar granules are organelles found in the terminally differentiating cells of keratinizing epithelia, and desmosomes are intercellular junctions in vertebrate epithelial cells, thus indicating that N-glycosylation of tissue-specific glycoproteins may contribute to increase the relative proportion of high mannose glycans. The striking roles of lysosomal enzymes in epidermis during lipid remodeling and desquamation may also reflect the observed high abundance of high mannose glycans.
  • K Takaya, N Nagahori, M Kurogochi, T Furuike, N Miura, K Monde, YC Lee, SI Nishimura
    JOURNAL OF MEDICINAL CHEMISTRY 48 (19) 6054 - 6065 0022-2623 2005/09 [Not refereed][Not invited]
     
    An affinity labeling reagent, uridine 5'-(6-amino-{2-[(7-bromomethyl-2-naphthyl)methoxy-carbonylmethoxy]ethoxy}acetyl-6-deoxy-alpha-D-galactopyranosyl) diphosphate (1a), was designed on the basis of 3D docking simulation and synthesized to investigate the functional role of Trp310 residue located in the small loop near the active site of human recombinant galactosyltransferase (beta GalT-1). Mass spectrometric analysis revealed that the Trp310 residue of beta GalT1 can be selectively modified with the naphthylmethyl group of compound la at the C-3 position of the indole ring. This result motivated us to synthesize novel uridine-5'-diphosphogalactose (UDP-Gal) analogues as candidates for mechanism-based inhibitors for beta GalT-1. We found that uridine 5'-(6-O-[10-(2-naphthyl)-3,6,9-trioxadecanyl]-alpha-D-galactopyranosyl) diphosphate (2) is the strongest inhibitor (K-i = 1.86 mu M) against UDP-Gal (K-m = 4.91 mu M) among compounds reported previously. A cold spray ionization time-of-flight mass spectrometry study demonstrated that the complex of this inhibitor and beta GalT-1 cannot interact with an acceptor substrate in the presence of Mn2+.
  • K Monde, T Taniguchi, N Miura, P Kutschy, Z Curillova, M Pilatova, J Mojzis
    BIOORGANIC & MEDICINAL CHEMISTRY 13 (17) 5206 - 5212 0968-0896 2005/09 [Refereed][Not invited]
     
    Synthesized by an efficient one-pot spirocyclization method, two chiral cruciferous phytoalexins, 1-methoxyspirobrassinin (2) and 1-methoxyspirobrassinol methyl ether (4a), were prepared through optical resolution using the chiral HPLC method of corresponding racemates. The absolute configuration of natural (+)-2 was elucidated as R by using the direct comparison of ECD and VCD spectra with those of known (S)-(-)-spirobrassinin (1). Another chiral phytoalexin, (-)-4a, had its absolute configuration 2R,3R elucidated through the comparison of observed and calculated VCD. Interestingly, the absolute configurations of natural (S)(-)-spirobrassinin (1) and (R)-(+)-1-methoxyspirobrassinin (2) were opposite of each other, even though their structures are almost similar, with the exception of an N-methoxy group. A significant difference in the antiproliferative activity between (2R,3R)-(-) and (2S,3S)-(+)-4a was observed. (c) 2005 Elsevier Ltd. All rights reserved.
  • K Niikura, R Kamitani, M Kurogochi, R Uematsu, Y Shinohara, H Nakagawa, K Deguchi, K Monde, H Kondo, SI Nishimura
    CHEMISTRY-A EUROPEAN JOURNAL 11 (13) 3825 - 3834 0947-6539 2005/06 [Not refereed][Not invited]
     
    We have developed an effective and practical trap-and-release method based on chemoselective ligation of carbohydrates with reactive aminooxyl groups attached to the surface of nanoparticles (referred to as glycoblotting nanoparticles). These glycoblotting nanoparticles were synthesized by UV irradiation of diacetylene-functionalized lipids that contain the aminooxyl group. The glycoblotting nanoparticles captured carbohydrates in aqueous solution under mild conditions and were collected by simple centrifugation. ne trapped carbohydrates were effectively released from the nanoparticles under acidic conditions to give pure oligosaccharides. This glycoblotting process reduced the time required for the purification process of carbohydrates to less than 6 h, compared to the several days needed for conventional chromatographic techniques. The oligosaccharides (N-glycan) were released from ovalbumin (glyco-protein) by PNGaseF after tryptic digestion. MALDI-TOF mass spectra before purification did not show any significant signals corresponding to N-glycans because these signals were hidden by the large signals of the abundant peptides. However, after purification with the glycoblotting nanoparticles, only signals corresponding to oligosaccharides appeared. We also demonstrated a clear analysis of the oligosaccharides contained in the mice dermis by means of glycoblotting.
  • M Pilatova, M Sarissky, P Kutschy, A Mirossay, R Mezencev, Z Curillova, M Suchy, K Monde, L Mirossay, J Mojzis
    LEUKEMIA RESEARCH 29 (4) 415 - 421 0145-2126 2005/04 [Not refereed][Not invited]
     
    We tested antiproliferative activity of selected cruciferous phytoalexins including brassinin, 1-methoxybrassinin, (+/-)-spirobrassin, (+/-)1-methoxyspirobrassinin and (+/-)-1-methoxyspirobrassinol, in leukemic Jurkat cell. The most effective of the tested phytoalexins was Imethoxybrassinin with IC50 10 mu mol 1(-1). However, significant effect of all phytoalexines was also determined at concentration 1 mu mol 1(-1). In 1-methoxybrassinin-treated Jurkat cells, we found significant increase in the fraction of cells with a sub-G(0)/G(1) DNA content, which is considered to be a marker of cell death by apoptosis. Apoptosis was also confirmed by the annexin V staining. In summary, 1-methoxybrassinin exerted potent antiproliferative activity probably due to cell cycle arrest and apoptosis induction. (c) 2004 Elsevier Ltd. All rights reserved.
  • MHC Resurreccion-Magno, IM Villasenor, N Harada, K Monde
    PHYTOTHERAPY RESEARCH 19 (3) 246 - 251 0951-418X 2005/03 [Not refereed][Not invited]
     
    2',4'-Dihydroxy-3',5'-dimethyl-6'-methoxychalcone 1, its isomeric flavanone 5-O-methyl-4'-desmethoxymatteucinol 2 and 2'4'-dihydroxy-6'-methoxy-3'-methylchalcone 3 were isolated from the leaves of S. samarangense using a bioassay-directed scheme. In an oral glucose tolerance test, at a dosage of 1.0 mg/20 g mouse, 1 and 2 significantly (alpha = 0.05) lowered the blood glucose levels (BGLs) in glucose-hyperglycaemic mice when administered 15 min after a glucose load. When co-administered with glucose, only 1 showed a significant lowering of BGLs 45 min after its oral administration. When administered 15 min before glucose, none of the flavonoids showed a positive effect. Only 1 decreased significantly, at alpha = 0.05, the BGLs of alloxan-diabetic mice at t = 90-150 min. Copyright (c) 2005 John Wiley & Sons, Ltd.
  • S Yamane, N Iwasaki, T Majima, T Funakoshi, T Masuko, K Harada, A Minami, K Monde, S Nishimura
    BIOMATERIALS 26 (6) 611 - 619 0142-9612 2005/02 [Not refereed][Not invited]
     
    In this study, we hypothesized that hyaluronic acid could provide superior biological effects on the chondrocytes in a three-dimensional culture system. To test this hypothesis, we investigated the in vitro behavior of rabbit chondrocytes oil a novel chitosan-based hyaluronic acid hybrid polymer fiber. The goal of the current study was to show the Superiority of this novel fiber as a scaffold biomaterial for cartilage tissue engineering. Chitosan polymer fibers (chitosan group) and chitosan-based hyaluronic acid hybrid polymer fibers (HA 0.04% and HA 0.07% groups, chitosan coated with hyaluronic acid 0.04% and 0.07%, respectively) were originally developed by the wetspinning method. Articular chondrocytes were isolated from Japanese white rabbits and cultured in the sheets consisting of each polymer fiber. The effects of each polymer fiber oil cell adhesivity, proliferation, morphological changes. and synthesis of the extracellular matrix were analyzed by quantitative a cell attachment test, DNA quantification, light and scanning electron microscopy, semi-quantitative RT-PCR, and immunohistochemical analysis. Cell adhesivity, proliferation and the synthesis of agrecan were significantly higher in the hybrid fiber (HA 0.04% and 0.07%) groups than in the chitosan group. On the cultured hybrid polymer materials, scanning electron microscopic observation showed that chondrocytes proliferated while maintaining their morphological phenotype and with a rich extracellular matrix synthesis around the cells. Immunohistochemical staining with an anti-type II collagen antibody demonstrated rich production of the type II collagen in the pericellular matrix from the chondrocytes. The chitosan-based hyaluronic acid hybrid polymer fibers show great potential as a desirable biomaterial for cartilaginous tissue scaffolds. (C) 2004 Elsevier Ltd. All rights reserved.
  • T Furuike, R Sadamoto, K Niikura, K Monde, N Sakairi, SI Nishimura
    TETRAHEDRON 61 (7) 1737 - 1742 0040-4020 2005/02 [Not refereed][Not invited]
     
    An efficient and practical method for the large-scale synthesis of an anti-inflammatory glycocluster having seven sialyl Lewis X (SLeX) residues was established on the basis of chemical and enzymatic strategy from beta-cyclodextrin (beta-CD) as a key starting scaffold material. A key intermediate, beta-CD derivative having seven N-acetyl-D-glucosamine (GlcNAc) residues [(GlcNAc)(7)CD], was prepared by a coupling reaction with heptakis 6-deoxy-6-iodo-beta-cyclodextrin and sodium thiolate containing a GlcNAc residue. Subsequent sugar elongation reactions of (GlcNAc)(7)CD proceeded smoothly by means of beta-1,4-galactosyltransferase, alpha-2,3-sialyltransferase, and alpha-1,3-fucosyltransferase V in the presence of the corresponding sugar nucleotides (UDP-Gal, CMP-Neu5Ac, and GDP-Fuc) and allowed to give a mono-dispersed glycodendrimer (M-w = 7924.5, calcd for C301H490N21O196S7Na7; MALDI-TOF MS, m/z 7946 [M + Na](+)) that completely substituted with seven SLeX branches at C-6 positions in excellent overall yield (74%, 3 steps). Hyper-branched glycodendrimer, (SLeX)(7)CD, exhibited highly amplified inhibitory effect on the interaction of E-selectin with SLeXn-BSA immobilized on the sensor chip by means of surface plasmon resonance method. (C) 2004 Elsevier Ltd. All rights reserved.
  • SI Nishimura, K Niikura, M Kurogochi, T Matsushita, M Fumoto, H Hinou, R Kamitani, H Nakagawa, K Deguchi, N Miura, K Monde, H Kondo
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 (1) 91 - 96 1433-7851 2005 [Not refereed][Not invited]
  • SI Nishimura, N Nagahori, K Takaya, Y Tachibana, N Miura, K Monde
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 (4) 571 - 575 1433-7851 2005 [Not refereed][Not invited]
  • S Abe, H Moriyama, K Niikura, F Fei, K Monde, S Nishimura
    TETRAHEDRON-ASYMMETRY 16 (1) 15 - 19 0957-4166 2005/01 [Not refereed][Not invited]
     
    Oxylamine-functionalized fullerene derivatives have been synthesized in order to attach oligosaccharides to the fullerene surface by simple chemical ligation. This method greatly simplifies the synthetic process for a variety Of oligosaccharide-containing fullerenes without any complicated chemical modification. (C) 2004 Elsevier Ltd. All rights reserved.
  • Y Takegawa, K Deguchi, S Ito, S Yoshioka, A Sano, K Yoshinari, K Kobayashi, H Nakagawa, K Monde, SI Nishimura
    ANALYTICAL CHEMISTRY 76 (24) 7294 - 7303 0003-2700 2004/12 [Not refereed][Not invited]
     
    2-Aminopyridine (PA)-derivatized oligosaccharides from IgG were analyzed by using reversed-phase HPLC/mass spectrometry (RP-HPLC/MS) and a MSn spectral library, in particular, focusing on two pairs of isomers incompletely separated or coeluted in chromatograms. We previously reported that MSn spectral matching considering both major fragment ions (m/z) and intensities is useful and applicable to the structural assignment of PA-oligosaccharide isomers. In this study, MSn spectral matching based on the MSn spectral library was applied to the assignment of these PA-oligosaccharide isomers in IgG. Its usefulness was investigated by comparing it to the conventional two-dimensional mapping method based on retention time indexes. Specifically, we focus on the assignment and quantification of the isomers, which are coeluted in chromatograms. From this, we propose a new method using MSn spectral matching and the working curve on which are plotted the relative intensities of selected fragment ions in their MS2 spectra versus various mixtures of the isomers. This new method demonstrated that the obtained quantities coincide very well with those estimated after separating by a combination of lectin and reversed-phase columns. This means that separation by RP-HPLC/MS is greatly simplified because complete separation of the isomers is no longer required. Application of this new method was tested by using the two other pairs of fucosylated and nonfucosylated PA-oligosaccharides from IgG. The results showed that this method works for them as well.
  • Masaaki Sato, Tetsuya Furuike, Reiko Sadamoto, Naoki Fujitani, Taku Nakahara, Kenichi Niikura, Kenji Monde, Hirosato Kondo, Shin-Ichiro Nishimura
    Journal of the American Chemical Society 126 (43) 14013 - 14022 0002-7863 2004/11/03 [Not refereed][Not invited]
     
    Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by α2,6-sialyltransferase (α2,6-SiaT) via an accessible glutamine residue at the N-terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc-Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N-acetyllactosamines, respectively, were administered to hyperglycemic mice. Both branched glycoinsulins showed prolonged glucose-lowering effects compared to native or lactose-carrying insulins, showing that sialic acid is important in obtaining a prolonged effect. Sia2,6-tri-LacNAc-Ins(B-F1Q), in particular, induced a significant delay in the recovery of glucose levels.
  • T Taniguchi, K Monde, N Miura, S Nishimura
    TETRAHEDRON LETTERS 45 (46) 8451 - 8453 0040-4039 2004/11 [Not refereed][Not invited]
     
    Novel vibrational circular dichroism (VCD) studies in the CH region of a series of methyl glycosidic carbohydrates were examined. The specific CH stretching VCD band predicts absolute stereochemistries of their anomeric positions. The C-1 chiral information was extracted to the methoxy substituent as a probe. The concept of the vibrational chirality probe from a single chiral center in the presence of numerous such centers might be useful in determining the absolute configuration, when a multiplicity of chiral centers is present in a molecule such as a carbohydrate. (C) 2004 Elsevier Ltd. All rights reserved.
  • M Sato, T Furuike, R Sadamoto, N Fujitani, T Nakahara, K Niikura, K Monde, H Kondo, SI Nishimura
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 (43) 14013 - 14022 0002-7863 2004/11 [Refereed][Not invited]
     
    Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by alpha2,6-sialyltransferase (alpha2,6-SiaT) via an accessible glutamine residue at the N-terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc-Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N-acetyllactosamines, respectively, were administered to hyperglycemic mice. Both branched glycoinsulins showed prolonged glucose-lowering effects compared to native or lactose-carrying insulins, showing that sialic acid is important in obtaining a prolonged effect. Sia2,6-tri-LacNAc-lns(B-F1Q), in particular, induced a significant delay in the recovery of glucose levels.
  • Y Tachibana, K Monde, SI Nishimura
    MACROMOLECULES 37 (18) 6771 - 6779 0024-9297 2004/09 [Not refereed][Not invited]
     
    Practical and versatile methods for the preparation of glycopeptide polymers containing base labile moieties were established by use of 1-isobuthoxycarbonyl-2-isobuthoxy-1,2-dihydroquinoline (IIDQ) or 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as polycondensation agents of glycopeptide units without any protection on the carbohydrate residues. These methods were applied for the synthesis of mucin-like glycoprotein mimics related to antifreeze glycoproteins (AFGPs), giving the target O-acetylated glycopolypeptides efficiently, while the conventional DPPA (diphenylphosphoryl azide) method gave complex mixtures of acyl migrated compounds.
  • K Monde, T Taniguchi, N Miura, SI Nishimura
    J. Am. Chem. Soc. 126 (31) 9496 - 9497 0002-7863 2004/08 [Refereed][Not invited]
  • T Ueda, F Feng, R Sadamoto, K Niikura, K Monde, SI Nishimura
    ORGANIC LETTERS 6 (11) 1753 - 1756 1523-7060 2004/05 [Not refereed][Not invited]
     
    4-Fluorinated UDP-MurNAc pentapeptide, 2, has been synthesized. In our previous study, UDP-MurNAc pentapeptide analogue 1 was found to be incorporated into the bacterial cell wall through biosynthesis. Compound 2 showed growth-inhibition activity against Gram-positive bacteria when it was added to growth media at 0.01 mg/mL.
  • N Iwasaki, ST Yamane, T Majima, Y Kasahara, A Minami, K Harada, S Nonaka, N Maekawa, H Tamura, S Tokura, M Shiono, K Monde, SI Nishimura
    BIOMACROMOLECULES 5 (3) 828 - 833 1525-7797 2004/05 [Not refereed][Not invited]
     
    The ideal cell-carrier material for cartilage regeneration should be one that closely mimics the natural environment in a living articular cartilage matrix. In the current study, we considered that alginate-based chitosan hybrid biomaterials could provide excellent supports for chondrocyte adhesion. To test this hypothesis, we investigated the adhesion behavior of rabbit chondrocytes onto an alginate polymer versus the adhesion of the chondrocytes onto some alginate-based chitosan hybrid polymer fibers in vitro. We demonstrated that the alginate-based chitosan hybrid polymer fibers showed much improved adhesion capacity with chondrocytes in comparison with alginate polymer fiber. Additionally, morphologic studies revealed maintenance of the characteristic round morphology of the chondrocyte and the dense fiber of the type II collagen produced by the chondrocytes in the hybrid polymer. On the basis of these results, we conclude that an alginate-based chitosan hybrid polymer fiber has considerable potential as a desirable biomaterial for cartilage tissue scaffolds.
  • R Sadamoto, K Niikura, T Ueda, K Monde, N Fukuhara, SI Nishimura
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 126 (12) 3755 - 3761 0002-7863 2004/03 [Not refereed][Not invited]
     
    UDP-MurNAc-pentapeptide derivative bacterial cell-wall precursors were synthesized as effective tools for surface display on living bacteria. Lactobacilli were incubated in the ketone-modified precursor-containing medium, and the ketone moiety was displayed on the bacterial surface through cell-wall biosynthesis. Oligomannose was coupled with the ketone moiety on the bacterial surface via a aminooxyl linker, thereby displaying this oligosaccharide on the surface of the bacteria. The increase in the adhesion of the sugar-displaying bacteria onto a concanavalin A-attached film compared to that of native bacteria was confirmed by microscopic observation and surface plasmon resonance measurement. The incorporation of the artificial cell-wall precursors was enhanced when incubated with fosfomycin, an inhibitor of cell-wall precursor biosynthesis.
  • H Hoshi, H Nakagawa, S Nishiguchi, K Iwata, K Niikura, K Monde, SI Nishimura
    JOURNAL OF BIOLOGICAL CHEMISTRY 279 (4) 2341 - 2349 0021-9258 2004/01 [Not refereed][Not invited]
     
    The Class I hyaluronan synthase ( HAS) is a unique glycosyltransferase synthesizing hyaluronan ( HA), a polysaccharide composed of GlcUA and GlcNAc, by using one catalytic domain that elongates two different monosaccharides. As for the synthetic mechanism, there are two alternative manners for the sugar elongation process. Some bacterial HASs add new sugars to the non-reducing end of the acceptor to grow polymers. On the other hand, some vertebrate enzymes seem to transfer sugars to the reducing end. Expression of vertebrate HASs as active and soluble proteins will accelerate further precise insight into mechanisms of sugar elongation reactions by natural HASs. Since large scale production of HA polymers and oligomers would become powerful tools both for basic studies and new biotechnology to create functional carbohydrates in medicinal purposes, advent of an efficient method for the expression of HASs in Escherichia coli is strongly expected. Here we communicate the first success of the production of recombinant human HAS2 proteins composed of only the catalytic region in E. coli as the active form. It was demonstrated that an engineered HAS2 expressed in E. coli exhibited significant activity to synthesize a mixture of HAS oligomers from 8-mer (HA8) to 16-mer (HA16). Engineered HAS2 prepared herein elongated sugars from exogenous tetrasaccharide to form polymers with a direction to the non-reducing end. According to the present results, large scale production of engineered recombinant HASs is to be performed using E. coli that will provide practical and economic advantages in manufacturing enzymes for use in the synthesis of various oligomeric HA molecules and their industrial applications.
  • Y Tachibana, GL Fletcher, N Fujitani, S Tsuda, K Monde, SI Nishimura
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43 (7) 856 - 862 1433-7851 2004 [Not refereed][Not invited]
  • M Sato, R Sadamoto, K Niikura, K Monde, H Kondo, SI Nishimura
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 43 (12) 1516 - 1520 1433-7851 2004 [Not refereed][Not invited]
  • Y Takegawa, S Ito, S Yoshioka, K Deguchi, H Nakagawa, K Monde, SI Nishimura
    RAPID COMMUNICATIONS IN MASS SPECTROMETRY 18 (4) 385 - 391 0951-4198 2004 [Not refereed][Not invited]
     
    Two isomeric pairs of 2-aminopyridine (PA)-derivatized fucosylated and non-fucosylated oligosaccharides (complex-type N-glycans of IgG) were analyzed using liquid chromatography/ion trap mass spectrometry (LC/ITMS) with a sonic spray ionization source and by varying the collision-induced dissociation voltage. Reproducibility of MSn (n = 2) spectra obtained by LC/ITMS was tested considering both fragment ions (m/z) and intensities. A comparison of their MSn spectra and evaluation of similarities (or matching), based on correlation coefficients between MSn spectra, was investigated as a possibility for structural assignment of the isomers. It is shown that such MSn spectral matching is useful and applicable to the structural assignment of relatively large fucosylated and sialylated PA-oligosaccharides released from IgG based on Bn- and Yn-type fragmentations of the corresponding [M+H+Na](2+) ions. Copyright (C) 2004 John Wiley Sons, Ltd.
  • K Niikura, N Osuga, N Nagahori, R Sadamoto, M Shiono, N Iwasaki, K Monde, A Minami, SI Nishimura
    POLYMER JOURNAL 36 (3) 209 - 218 0032-3896 2004 [Not refereed][Not invited]
     
    We prepared sugar-displayed fluorescent nanoparticles using photopolyinerization of the vesicles of diacetylene-containing glycolipids. After photopolymerization, the nanoparticles exhibited fluorescent emission at 400-600 nm upon excitation at 380 nm. The binding of sugar-recognizing proteins (lectins) onto the fluorecent nanoparticles induced changes in fluorescence. The fluorescent intensity of the nanoparticles decreased with an increase in lectin concentration. On the contrary, the enzymatic release of oligosaccharides from the glyconanoparticles gave an increase in fluorescence. Using a phosphatidylcholine-type lipid as the matrix lipid of the nanoparticles, the non-specific adsorption of lectins on the surface was drastically restricted, leading to the generation of a specific response to the target proteins.
  • F Feng, K Okuyama, K Niikura, T Ohta, R Sadamoto, K Monde, T Noguchi, SI Nishimura
    ORGANIC & BIOMOLECULAR CHEMISTRY 2 (11) 1617 - 1623 1477-0520 2004 [Not refereed][Not invited]
     
    Two non-natural. uorinated 2-N-acetamidosugar nucleotides, uridine 5'-diphosphate (UDP) 2-acetamido-2,4-dideoxy-4-fluoro-alpha-D-glucopyranose (UDP-4-FGlcNAc) 1 and its galacto isomer (UDP-4-FGalNAc) 2, were enzymatically constructed by treating chemically synthesized. uorinated 2-N-acetamidosugar 1-phosphates as the donor with UDP 2-acetamido-2-deoxy-alpha-D-glucopyranose pyrophosphorylase in the presence of uridine 5'-triphosphate (UTP).
  • SI Nishimura, N Nagahori, R Sadamoto, K Monde, K Niikura
    SYNTHESIS OF CARBOHYDRATES THROUGH BIOTECHNOLOGY 873 113 - 124 0097-6156 2004 [Refereed][Not invited]
     
    Enzymatic synthesis is potential method for the construction of glycoconjugates as well as conventional chemical synthesis. Use of glycosyltransferases in the synthetic schemes has accelerated practical synthesis of oligosaccharides and related compounds. However, there is no systematic approach for establishing "automated glycosynthesizer" based on the combined chemical and enzymatic strategy. We have found that water-soluble glycopolymers bearing multivalent sugars become excellent glycosyl acceptor substrates of glycosyltransferases. Affinity of enzymes with multivalent glycosyl acceptors was drastically enhanced by polymeric sugar-cluster effect. Some designed linkers that can be recognized by specific enzyme permitted release of products from polymer supports under mild and selective conditions. By employing these water-soluble primers with some engineered glycosyltransferases, we succeeded to produce "artificial Golgi apparatus", an automatic glycosynthesizer controlled by computer. In this chapter, our recent approach for direct monitoring of sugar -elongation reactions by using surface plasmon resonance (SPR) method will be described, since direct and real time monitoring of enzymatic carbohydrate synthesis is strongly required for materializing practically usable artificial Golgi apparatus. (C) 2004 American Chemical Society.
  • K Monde, T Taniguchi, N Miura, SI Nishimura, N Harada, RK Dukor, LA Nafie
    TETRAHEDRON LETTERS 44 (32) 6017 - 6020 0040-4039 2003/08 [Not refereed][Not invited]
     
    Cruciferous phytoalexin related metabolites, (-)-dioxibrassinin (1) and (-)-3-cyanomethyl-3-hydroxyoxindole (2) were prepared from isatin as racemates and were resolved by chiral HPLC. Their absolute configurations were determined by the new chiroptical technique, vibrational circular dichroism (VCD), as well as by the conventional electronic circular dichroism (ECD). It is concluded that the absolute configurations of the naturally occurring (-)-1 and (-)-2 are both S. (C) 2003 Elsevier Ltd. All rights reserved.
  • N Nagahori, K Niikura, R Sadamoto, M Taniguchi, A Yamagishi, K Monde, SI Nishimura
    ADVANCED SYNTHESIS & CATALYSIS 345 (6-7) 729 - 734 1615-4150 2003/06 [Not refereed][Not invited]
     
    beta(1-->4) Galactosyltransferase expressed as a fusion protein with maltose binding protein (MBP-GalT) was displayed specifically on a Langmuir-Blodgett (LB) membrane prepared by photopolymerization of maltotriose-carrying glycolipid (1) with 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (2). The catalytic activity of MBP-GalT on the LB film was directly monitored by the surface plasmon resonance (SPR) method using a GlcNAc-carrying water-soluble polymer (3) as an acceptor substrate. Highly sensitive sigmoidal-type signals were obtained upon the addition of the acceptor substrate in the presence of the donor substrate, UDP-galactose (UDP-Gal), while the binding of 3 was not detected in the absence of UDP-Gal. The intensities of the signals were dependent on the amount of immobilized MBP-GalT on the LB film, which was estimated from the images obtained by atomic force microscope (AFM).
  • T Furuike, K Yamada, T Ohta, K Monde, SI Nishimura
    TETRAHEDRON 59 (27) 5105 - 5113 0040-4020 2003/06 [Not refereed][Not invited]
     
    An efficient and versatile method for the synthesis of a biantennary octasaccharide derivative was established by combined chemical and enzymatic manipulations of 1,6-anhydro-beta-lactose as a key starting material. A key 1,6-anhydro-beta-lactose derivative having two unprotected hydroxyl groups at C-3' and C-6' positions was prepared and employed for the chemical coupling reaction with a known 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl imidate to afford a tetrasaccharide derivative with two GlcNAc branches in 69% yield. Enzymatic galactosylation using UDP-Gal with a bovine milk beta1,4-galactosyltransferase and subsequent sialylation with a recombinant alpha,2,3-sialyltransferase in the presence of CMP-Neu5Ac proceeded smoothly and gave a desired model compound, a bivalent sialooctasaccharide (1), in 73% overall yield from the tetrasaccharide intermediate. (C) 2003 Elsevier Science Ltd. All rights reserved.
  • N Nagahori, K Niikura, R Sadamoto, K Monde, SI Nishimura
    AUSTRALIAN JOURNAL OF CHEMISTRY 56 (6) 567 - 576 0004-9425 2003 [Not refereed][Not invited]
     
    Photopolymerizable glycolipids incorporating ceramide- or amido-type linkers and able to form stable monolayers were efficiently synthesized by chemical and enzymatic methods. Glycolipid polymer films served as platforms for the immobilization of proteins through specific carbohydrate - protein interactions at the air - water interface. Carbohydrate-binding proteins deposited on the glycolipid film were observed by atomic force microscopy, which showed varying submicron-sized protein patterns such as dendrites, dots, and networks, depending on the lipid structure, membrane preparation process, and sugar density of the membrane. Surface plasmon resonance measurement confirmed that the subunit-type lectins immobilized on the glycolipid membranes exhibited the ability to interact specifically with carbohydrate ligands by using unoccupied binding sites.
  • T Ohta, N Miura, N Fujitani, F Nakajima, K Niikura, R Sadamoto, CT Guo, T Suzuki, Y Suzuki, K Monde, SI Nishimura
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 42 (42) 5186 - 5189 1433-7851 2003 [Not refereed][Not invited]
  • Sadamoto R, Niikura K, Monde K, Nishimura S
    Methods in enzymology 362 273 - 286 0076-6879 2003 [Refereed][Not invited]
  • Y Tachibana, N Matsubara, F Nakajima, T Tsuda, S Tsuda, K Monde, SI Nishimura
    TETRAHEDRON 58 (51) 10213 - 10224 0040-4020 2002/12 [Not refereed][Not invited]
     
    An efficient synthetic method of sequential glycopeptide-polymer by means of the combined chemical and enzymatic strategy was applied to the practical synthesis of some tandem repeating mucin-type glycoproteins. Versatility of the present synthetic strategy was demonstrated by elucidating some physicochemical and conformational analyses of these synthetic mucins. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • P Kutschy, M Suchy, K Monde, N Harada, R Maruskova, Z Curillova, M Dzurilla, M Miklosova, R Mezencev, J Mojzis
    TETRAHEDRON LETTERS 43 (52) 9489 - 9492 0040-4039 2002/12 [Not refereed][Not invited]
     
    The first syntheses of cruciferous indole phytoalexins (+/-)-1-methoxyspirobrassinin, (+/-)-1-methoxyspirobrassinol, (+/-)-1-methoxyspirobrassinol methyl ether as well as a new syntheses of phytoalexins (+/-)-spirobrassinin and cyclobrassinin were achieved by dioxane dibromide (DDB)-mediated spirocyclization of brassinin and its I-substituted derivatives. (C) 2002 Elsevier Science Ltd. All rights reserved.
  • R Sadamoto, K Niikura, PS Sears, HT Liu, CH Wong, A Suksomcheep, F Tomita, K Monde, SI Nishimura
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 124 (31) 9018 - 9019 0002-7863 2002/08 [Not refereed][Not invited]
  • K Yoshida, S Osawa, K Monde, M Watanabe, N Harada
    ENANTIOMER 7 (1) 23 - 32 1024-2430 2002/01 [Not refereed][Not invited]
     
    To determine the absolute configuration of chiral fullerene bis-adducts, we have studied the double Bingel reaction of C-60 with chiral tether (2S,3S)-(-)-9 derived from (R,R)-(+)-tartaric acid, and have succeeded in isolating two possible chiral bis-adducts 10a (5%) and 10b (2%) in addition to the C-s-symmetrically added derivative 10c (40%). The CD spectra of chiral bis-adducts [CD(+)281]-10a and [CD(-)281]-10b show very intense Cotton effects, which are almost of mirror image, indicating that their chiral C-60 pi-electron systems are enantiomeric each other. The H-1 and C-13 NMR spectra of 10a and 10b indicate that they have C-2-symmetrical structures, and the vicinal coupling constants between two equivalent protons H-2 and H-2' were determined as 1.2 Hz for 10a and 1.8 Hz for 10b, respectively by the 13 C satellite band method. From the conformational analyses, the absolute configurations of these chiral C60 fullerene bis-adducts were unambiguously determined as [CD(+)281]-(S,S,C-f)-10a and [CD(-)281]-(S,S,(f)A)-10b, respectively.
  • T Sukegawa, T Furuike, K Niikura, A Yamagishi, K Monde, SI Nishimura
    CHEMICAL COMMUNICATIONS 430 (5) 430 - 431 1359-7345 2002 [Not refereed][Not invited]
     
    A novel class of sulfated glycolipids with excellent self-assembling capacity to form stable monolayers at an air-water interface and specific erythrocyte-like liposomes was synthesised from alpha, beta, and gamma-cyclodextrins as starting materials.
  • ML Gilchrist, K Monde, Y Tomita, T Iwashita, K Nakanishi, AE McDermott
    JOURNAL OF MAGNETIC RESONANCE 152 (1) 1 - 6 1090-7807 2001/09 [Not refereed][Not invited]
     
    F-19 homonuclear dipolar recoupling methods were used to measure internuclear distances ranging from 5 to 12 Angstrom in fluorinated organic compounds in the solid state. Magic-angle-spinning-based high-resolution techniques were utilized. Trifluoromethyl and aromatic fluorine groups were seperated by rigid aromatic spacers; these compounds were diluted into nonfluorinated host molecule matrices to give isolated homonuclear spin pairs with known internuclear distances. Radiofrequency-driven recoupling (RFDR) was used to elicit magnetization exchange between the spin pairs in 1D and 2D experiments. Simulation of the exchange was accomplished using a Monte Carlo-type algorithm to search the parameter space. These methods allow the determination of distances with an accuracy of 1 Angstrom at shorter distances and 2 Angstrom at longer distances, with the assumption of no prior knowledge of T-2(ZQ). (C) 2001 Academic Press.
  • M Suchy, P Kutschy, K Monde, H Goto, N Harada, M Takasugi, M Dzurilla, E Balentova
    JOURNAL OF ORGANIC CHEMISTRY 66 (11) 3940 - 3947 0022-3263 2001/06 [Not refereed][Not invited]
     
    Stereochemical studies of a cruciferous oxindole phytoalexin, (S)-(-)-spirobrassinin [(-)-4], and its oxazoline analogue, spirooxazoline (11), were carried out. Racemic spirobrassinin [(+/-)-4] was synthesized by SOCl2- or MsCl-mediated cyclization of dioxibrassinin [(+/-)-8], Treatment of ( 3-hydroxyoxindol-3-yl)methylammonium chloride [(+/-)-9] with CSCl2 and subsequent methylation of the obtained spirooxazolidinethione (+/-)-10 afforded spirooxazoline [(+/- )11]. Enantioresolution of (+/-)-4 and (+/- )11 was achieved by derivatization with (S)-(-)-1-phenylethyl isocyanate (12), chromatographic separation of diastereomeric amides 13, 14 or 15, 18, and their cleavage with CH3ONa. Absolute configuration of the stereogenic center in natural (S)-(-)-4 was derived from the exciton, calculated via CD methods, and unequivocally confirmed by X-ray crystallographic analyses of 1-[1 'S,4 'R-(-)-camphanoyl] derivatives [(-)-19 and (-)-20] of (+/-)- and (-)-4. Novel enantiomeric enrichment phenomena of 4 and 11 were discovered during their chromatographic separations under achiral HPLC conditions. Screening of antifungal activity against the fungus Bipolaris leersiae revealed no significant dependence of this activity on absolute configuration.
  • K Monde, N Harada, M Takasugi, P Kutschy, M Suchy, M Dzurilla
    JOURNAL OF NATURAL PRODUCTS 63 (9) 1312 - 1314 0163-3864 2000/09 [Not refereed][Not invited]
     
    Enantiomeric purity of a cruciferous phytoalexin, spirobrassinin (1), was determined by chiral HPLC analysis,The enantiomeric excesses of two natural spirobrassinin fractions separated by nonchiral chromatography were considerably different. A significant enantiomeric enrichment was observed during the nonchiral chromatographic separation of an artificial enantiomeric mixture of 1.
  • K Monde, S Osawa, N Harada, M Takasugi, M Suchy, P Kutschy, M Dzurilla, E Balentova
    CHEMISTRY LETTERS 29 (8) 886 - 887 0366-7022 2000/08 [Not refereed][Not invited]
     
    Synthetic (+/-)-spirobrassinin (1) was enantioresolved by a chiral auxiliary method giving (+)-1 and natural (-)-1. The absolute configuration was unambiguously determined by X-ray crystallography of a (1'S,4'R)-camphanoyl derivative of (+)-1. Consequently, natural (-)-1 has an S configuration. Their CD spectra supported this result.
  • K Monde, Y Tomita, ML Gilchrist, AE McDermott, K Nakanishi
    ISRAEL JOURNAL OF CHEMISTRY 40 (3-4) 301 - 306 0021-2148 2000 [Not refereed][Not invited]
     
    With C-13-labeled samples, it is possible to measure internuclear distances up to 7 Angstrom by solid-state NMR, thus providing a powerful tool for probing ligand-receptor interactions. However, limitations in measurable distances and appreciable natural abundant C-13 background signals present problems in solid-state C-13 NMR. In order to overcome these disadvantages, a set of reference compounds with known F-F distances, namely, quinolinol, p-biphenyl, and p-terphenyl-bearing trifluoromethyl and trifluoromethylthio groups, have been synthesized. The preparation of these reference compounds and means for diluting these references in solid-state NMR are described.
  • Robert Baur, Erich Staedler, Kenji Monde, Mitsuo Takasugi
    CHEMOECOLOGY 8 (4) 163 - 168 0937-7409 1998/12 [Not refereed][Not invited]
     
    Bacteria species known to induce the biosynthesis of crucifer-specific phytoalexins have earlier been shown to be associated with Delia flies. Eleven crucifer-specific phytoalexins and related synthetic compounds were applied on surrogate paper leaves and offered to cabbage root flies in oviposition assays. Since three of these compounds (methoxybrassinin, cyclobrassinin, brassitin) proved to be significantly stimulatory whereas the remaining metabolites had no effect, the reaction of the fly appears to be structure-specific. Inactive phytoalexins had no inhibitory effect on oviposition. 100 mu g of methoxybrassinin per surrogate leaf was as stimulatory as 0.05 gle (gram leaf equivalent) of a methanolic host-leaf (Brassica oleracea) extract. Thus the three active phytoalexins can explain only part of the activity of host-pant extracts but might induce a preference for infected plants.
  • K Monde, H Satoh, M Nakamura, M Tamura, M Takasugi
    JOURNAL OF NATURAL PRODUCTS 61 (7) 913 - 921 0163-3864 1998/07 [Not refereed][Not invited]
     
    Seven chlorine-containing orcinol derivatives (2-8) and orcinol (9) have been isolated from diseased bulbs of the edible lily Lilium maximowiczii, and their structures have been elucidated. Six of the chlorinated orcinol derivatives (2, 4-8) showed antifungal activity. Because organochlorine compounds are rare in terrestrial higher plants, their biosynthetic origin was examined. These compounds were shown to be induced in intact bulb scales by UV irradiation or by inoculation with the pathogenic fungus Fusarium oxysporum f. sp. lilii. Biosynthetic studies suggested that these "natural organochlorine pesticides" are produced by enzymatic chlorination of orcinol (9) with chloroperoxidase and hydrogen peroxide, which are both induced in the plant tissue under stress conditions.
  • T Jin, K Monde
    CHEMICAL COMMUNICATIONS 1998 (13) 1357 - 1358 1359-7345 1998/07 [Not refereed][Not invited]
     
    An inherently fluorescent chiral calix[4]arene 2 with two pyrene moieties forming an intramolecular pyrene excimer has been synthesized and optically resolved by an HPLC method using a chiral-packed column.
  • K Monde, A Tanaka, M Takasugi
    JOURNAL OF ORGANIC CHEMISTRY 61 (25) 9053 - 9054 0022-3263 1996/12 [Not refereed][Not invited]
  • H Okuyama, K Monde
    CHEMISTRY AND PHYSICS OF LIPIDS 83 (2) 169 - 173 0009-3084 1996/09 [Not refereed][Not invited]
     
    The structure of an ornithine-containing lipid from Cytophaga johnsonae Stanier strain C21 was determined by H-1-NMR analysis of its major molecular species (compound 1) consisting of iso-3-hydroxy heptadecanoic (iso-3-OH-17:0) and iso-pentadecanoic acids (iso-15:0). The NOESY spectrum showed the cross peaks between alpha-NH of ornithine and two protons of the alpha-methylene moiety of iso-3-OH-17:0. The delta-amino group of the ornithine did not form an amide linkage with any fatty acid. Thus, the structure of the ornithine-containing lipid was iso-3-hydroxy heptadecanoic acid, alpha-amide linked to ornithine and esterified to iso-15:0.
  • Akira SHIRATA, Kazuhisa SUGAYA, Mitsuo TAKASUGI, Kenji MONDE
    Japanese Journal of Phytopathology 61 (5) 493 - 502 0031-9473 1995/10
  • K MONDE, M TAKASUGI, A SHIRATA
    PHYTOCHEMISTRY 39 (3) 581 - 586 0031-9422 1995/06 [Not refereed][Not invited]
     
    Three new brassinin related stress metabolites, named brassitin, N-methoxyspirobrassinol methyl ether and N-methoxyspirobrassinol, were isolated from the Japanese radish 'Daikon' (Raphanus sativus var. hortensis) after inoculation with Pseudomonas cichorii. Their structures have been established on the basis of spectroscopic data and chemical reactions. N-Methoxyspitobrassinol has an unusual hemi-aminal structure, and occurs as a mixture of diastereomers. The occurrence of N-methoxyspirobrassinol methyl ether and N-methoxyspirobrassinol suggests the involvement of oxidized intermediates in the biosynthesis from brassinin to spirobrassinin.
  • Kenji Monde, Kimio Tamura, Mitsuo Takasugi
    Phytochemistry 39 (3) 587 - 589 0031-9422 1995 [Not refereed][Not invited]
     
    Feeding experiments with Pseudomonas cichorii-inoculated Japanese radish roots indicated that methoxybrassinin is not derived from brassinin, and that cyclobrassinin is not biosynthesized from methoxybrassinin. © 1995.
  • RV PERSON, K MONDE, HU HUMPF, N BEROVA, K NAKANISHI
    CHIRALITY 7 (3) 128 - 135 0899-0042 1995 [Not refereed][Not invited]
     
    There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane-1,4-diols (both ee or ea) and a wide variety of 3-hydroxy carotenoids, 3-hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROM-CH=C=CH-COOH. The allenic bond introduces a 90 degrees twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases. (C) 1995 Wiley-Liss, Inc.
  • Kenji Monde, Mitsuo Takasugi
    Journal of Pesticide Science 20 (3) 339 - 343 1349-0923 1995 [Refereed][Not invited]
  • K MONDE, M TAKASUGI, T OHNISHI
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 116 (15) 6650 - 6657 0002-7863 1994/07 [Not refereed][Not invited]
     
    We report the results of biosynthetic studies on the sulfur-containing indole phytoalexins, antimicrobial compounds produced by plants after exposure to microorganisms. Feeding experiments with UV-irradiated sliced turnip root (Brassica campestris ssp. rapa) revealed that spirobrassinin (3) is formed via brassinin (1a) and that 1a is biosynthesized by the intramolecular rearrangement of L-tryptophan to form unstable indol-3-ylmethylisothiocyanate (10a). Trapping experiments of 10a with NaSCH3 and formation of PhCH(2)NH-CS-SCH3 (14) on administration of benzyl isothiocyanate supported the presence of the labile isothiocyanate intermediate. Feeding experiments of a mixture of L-[methyl-H-3(3)]methionine and L-[S-35]methionine revealed that the methylthio group of methionine is incorporated into 1a as an unusual intact unit. Incorporation of L-[S-35]cysteine into la and 3 indicated the origin of another sulfur atom. These studies suggest that the biosynthetic pathway of cruciferous phytoalexins is at least partially linked to one of the indole glucosinolates which are typical components of crucifers. Structures of metabolites of 2-methylbrassinin (16) imply the presence of an oxidized intermediate between 1a and other cruciferous phytoalexins.
  • Mitsuo Takasugi, Kenji Monde, Kimio Tamura, Kensuke Kobayashi, Masanori Somei
    HETEROCYCLES 38 (2) 263 - 263 0385-5414 1994
  • K MONDE, M KISHIMOTO, M TAKASUGI
    TETRAHEDRON LETTERS 33 (37) 5395 - 5398 0040-4039 1992/09 [Not refereed][Not invited]
     
    Infected lily bulbs afforded the first natural 3-benzylidene-1,4-benzodioxin-2(3H)-one derivative, yurinelide 1. The structure was elucidated by interpretation of the spectral data and chemical reactions.
  • Ryoh Kawazoe, Kenji Monde, Wolfgang Reichardt, Hidetoshi Okuyama
    Archives of Microbiology 158 (3) 171 - 175 0302-8933 1992/08 [Refereed][Not invited]
     
    Cytophaga johnsonae Stanier strain C21 (C. johnsonae C21) contains phosphatidylethanolamine (PE), an unusual glycine-containing lipid (glycine lipid), and two kinds of unidentified lipid as major lipid components. One of the latter lipids was identified by chemical and physicochemical methods as iso-3-hydroxy fatty acid, α-amide linked to ornithine and esterified to iso-nonhydroxy fatty acid (ornithine lipid). The other lipid was identified as a sulfonolipid by a tracer experiment using 35S. PE, glycine lipid and sulfonolipid were found in all seven species of Cytophage examined, namely, C. huchinsonii, C. heparina, C. johnsonae C21, C. aquatilis, and three unidentified species of Cytophaga. However, ornithine lipid was found only in the latter five species. By contrast, a serine-containing lipid, which is a specific lipid component of Flavobacterium species, was not found in any species of Cytophaga examined. The possible use and significance of amino acid-containing lipids and sulfonolipids as chemosystematic markers of the Cytophaga species are discussed. © 1992 Springer-Verlag.
  • K MONDE, M TAKASUGI
    JOURNAL OF CHROMATOGRAPHY 598 (1) 147 - 152 0021-9673 1992/05 [Not refereed][Not invited]
     
    A reversed-phase high-performance liquid chromatographic analysis of cruciferous phytoalexins, antimicrobial compounds synthesized de novo by plants after exposure to microorganisms, was performed using an acetonitrile-methanol-water complex solvent gradient system. A well resolved chromatogram of thirteen phytoalexins and three related indole metabolites isolated from cruciferous plants was obtained by this method. Accumulation of phytoalexins in Pseudomonas cichorii-inoculated turnip tissue was followed by this high-performance liquid chromatographic analysis.
  • K MONDE, M TAKASUGI
    JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS 1991 (22) 1582 - 1583 0022-4936 1991/11 [Not refereed][Not invited]
     
    Incorporation of [4'-H-2], [2-C-13]tryptophan, and [methyl-(H3)-H-2]brassinin 1 into spirobrassinin 3 by UV-irradiated turnip tissue indicates that spirobrassinin 3 is formed via brassinin 1, which is biosynthesized from tryptophan by a pathway involving a molecular rearrangement and possible formation of indol-3-ylmethyl isothiocyanate 6a.
  • K MONDE, M TAKASUGI, JA LEWIS, GR FENWICK
    ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES 46 (3-4) 189 - 193 0939-5075 1991/03 [Not refereed][Not invited]
     
    Sliced turnip root (Brassica campestris L. ssp rapa) was irradiated for a total of 20 min with a 15 W germicidal lamp and the tissue incubated at 25-degrees-C. The effects of such treatment on indole phytoalexins (methoxybrassinin (I); brassinin (II); cyclobrassinin (III); spirobrassinin (IV) and glucosinolates were determined using high performance liquid chromatography procedures. Accumulation of phytoalexins I-III was evident within 8 h of irradiation, whilst formation of spirobrassinin was evident only after 24 h. Maximal levels of III and IV (> 100-mu-g g-1 freeze dried tissue) were greater than those of I and II (27 and 17-mu-g g-1, respectively). The individual glucosinolate levels were affected in a complex manner; whilst most glucoinolates decreased on storage, the levels of indole glucosinolates, glucobrassicin (XI) and 1-methoxyglucobrassicin (XIII), increased until 5 to 6 days after irradiation and thereafter declined. Whilst structural features of I-IV, XI and XIII suggest close biosynthetic relationships between these classes of biologically-active indoles, further studies are needed to establish this point unambiguously.
  • K MONDE, K SASAKI, A SHIRATA, M TAKASUGI
    PHYTOCHEMISTRY 30 (9) 2915 - 2917 0031-9422 1991 [Not refereed][Not invited]
     
    Brassicanal C, a new sulphur-containing phytoalexin, and two dioxindoles were isolated from cabbage inoculated with Pseudomonas cichorii. Brassicanal C was shown to possess a unique sulphinate structure on the basis of spectroscopic data and optical activity. One of the dioxindoles, dioxibrassinin, appears structurally to be a possible precursor to spirobrassinin.
  • K MONDE, K SASAKI, A SHIRATA, M TAKASUGI
    PHYTOCHEMISTRY 30 (12) 3921 - 3922 0031-9422 1991 [Not refereed][Not invited]
     
    Two methoxybrassinin-related stress metabolites, named methoxybrassenins A and B, were isolated from Brassica oleracea var. capitata inoculated with Pseudomonas cichorii. Their structures have been elucidated by spectroscopic and chemical methods. The unusual NMR spectrum of methoxybrassenin B is also discussed in connection with its structure.
  • K MONDE, M TAKASUGI, N KATSUI, T MASAMUNE
    CHEMISTRY LETTERS 19 (8) 1283 - 1286 0366-7022 1990/08 [Not refereed][Not invited]
  • K MONDE, N KATSUI, A SHIRATA, M TAKASUGI
    CHEMISTRY LETTERS 19 (2) 209 - 210 0366-7022 1990/02 [Not refereed][Not invited]
  • Kenji Monde, Toyohisa Oya, Akira Shirata, Mitsuo Takasugi
    Phytochemistry 29 (11) 3449 - 3451 0031-9422 1990 [Not refereed][Not invited]
     
    A sesquiterpenoid phytoalexin, cichoralexin was isolated from Cichorium intybus inoculated with Pseudomonas cichorii. Its structure has been elucidated by spectroscopic methods. © 1990.
  • K MONDE, K SASAKI, A SHIRATA, M TAKASUGI
    PHYTOCHEMISTRY 29 (5) 1499 - 1500 0031-9422 1990 [Not refereed][Not invited]
  • M TAKASUGI, K MONDE, N KATSUI, A SHIRATA
    BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN 61 (1) 285 - 289 0009-2673 1988/01 [Not refereed][Not invited]
  • M TAKASUGI, S KAWASHIMA, K MONDE, N KATSUI, T MASAMUNE, A SHIRATA
    PHYTOCHEMISTRY 26 (2) 371 - 375 0031-9422 1987 [Not refereed][Not invited]
  • M TAKASUGI, K MONDE, N KATSUI, A SHIRATA
    CHEMISTRY LETTERS 16 (8) 1631 - 1632 0366-7022 1987 [Not refereed][Not invited]

MISC

  • 門出 健次  有機合成化学協会誌  82-  (2)  115  -115  2024/02
  • 門出 健次, 村井 勇太  生化学  92-  (2)  272  -277  2020/04  [Not refereed][Not invited]
  • Kenji Monde, Atsufumi Nakahashi, Nobuaki Miura, Tohru Taniguchi, Yoshihiro Yaguchi, Daisuke Sugimoto, Makoto Emura  ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY  248-  2014/08  [Not refereed][Not invited]
  • MONDE Kenji  高分子  61-  (10)  779  -780  2012/10/01
  • SATO HISAKO, TANIGUCHI TOORU, MONDE KENJI, FUKUDA YUTAKA, YAMAGISHI AKIHIKO  錯体化学討論会講演要旨集  57th-  192  2007/09/10  [Not refereed][Not invited]
  • Nobuaki Miura, Kazuko Hirose, Tomonori Ito, Ryo Hashimoto, Nobuhiro Fukushima, Kenji Monde, Shin-Ichiro Nishimura  GLYCOBIOLOGY  16-  (11)  1123  -1124  2006/11  [Not refereed][Not invited]
  • Hiroaki Nakagawa, Shinji Hayashi, Shigeaki Abe, Noriko Nagahori, Kenji Monde, Miki Ichikawa-Ohira, Hirosato Kondo, Shin-Ichi Akiyama, Kisaburo Deguchi, Akira Nakagawara, Shin-Ichiro Nishimura  GLYCOBIOLOGY  16-  (11)  1150  -1150  2006/11  [Not refereed][Not invited]
  • Kenji Monde, Tohru Taniguchi, Masami Fukuzawa, Mai Hashimoto, Atsufumi Nakahashi, Nobuaki Miura, Shin-Ichiro Nishimura  GLYCOBIOLOGY  16-  (11)  1136  -1137  2006/11  [Not refereed][Not invited]
  • SATO HISAKO, TANIGUCHI TOORU, MONDE KENJI, NISHIMURA SHIN'ICHIRO, YAMAGISHI AKIHIKO  錯体化学討論会講演要旨集  56th-  326  2006/09/08  [Not refereed][Not invited]
  • SATO HISAKO, TANIGUCHI TOORU, MONDE KENJI, NISHIMURA SHIN'ICHIRO, YAMAGISHI AKIHIKO  錯体化学討論会講演要旨集  56th-  34  2006/09/08  [Not refereed][Not invited]
  • LI Xuebing, WATANABE Shinya, SUZUKI Takashi, SUZUKI Yasuo, WATANABE Miho, NATORI Yasuhiro, NISHIKAWA Kiyotaka, KITA Eiji, MONDE Kenji, NISHIMURA Shin-Ichiro  キチン・キトサン研究 = Chitin and chitosan research  11-  (2)  120  -121  2005/07/01  [Not refereed][Not invited]
  • K Monde, T Taniguchi, N Miura, SI Nishimura  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY  127-  (16)  6133  -6133  2005/04  [Not refereed][Not invited]
  • Y Takegawa, S Ito, S Yoshioka, K Deguchi, H Nakagawa, K Monde, SI Nishimura  RAPID COMMUNICATIONS IN MASS SPECTROMETRY  19-  (4)  588  -588  2005  [Not refereed][Not invited]
  • T Taniguchi, N Miura, SI Nishimura, K Monde  MOLECULAR NUTRITION & FOOD RESEARCH  48-  (4)  246  -254  2004/09  [Not refereed][Not invited]
  • T Ueda, F Feng, R Sadamoto, K Niikura, K Monde, SI Nishimura  ORGANIC LETTERS  6-  (14)  2489  -2489  2004/07  [Not refereed][Not invited]
  • LI Xuebing, WATANABE Shinya, SUZUKI Takashi, SUZUKI Yasuo, NATORI Yasuhiro, NISHIKAWA Kiyotaka, MONDE Kenji, NISHIMURA Shin-Ichiro  キチン・キトサン研究 = Chitin and chitosan research  10-  (2)  204  -205  2004/07/01  [Not refereed][Not invited]
  • 佐藤公昭, 貞許礼子, 藤谷直樹, 中原拓, FENG F, 新倉謙一, 門出健次, 西村紳一郎, 近藤裕郷  高分子学会予稿集(CD-ROM)  53-  (1)  IH14  2004/05/10  [Not refereed][Not invited]
  • Taniguchi Tohru, Miura Nobuaki, Uchida Naoto, Nishimura Shin-Ichiro, Monde Kenji  Symposium on the Chemistry of Natural Products, symposium papers  46-  (0)  401  -406  2004  [Not refereed][Not invited]
     
    Chiral molecules exhibit circular dichroism (CD), the differential absorption of left versus right circularly polarized light, and the spectroscopies have been useful method for determining the absolute configuration. Recently, the measurement of CD in an infrared region, i.e. vibrational circular dichroism (VCD), has been advanced instrumentally and theoretically. VCD has some advantages over conventional electronic circular dichroism (ECD) by the applicability to all organic molecules and the reliability of ab initio quantum calculations. We apply this powerful technique to the determination of the absolute stereochemistry of some cruciferous phytoalexin-related compounds and to analysis of glycoconjugates. The determination of the absolute configuration of cruciferous phytoalexin-related compounds A number of cruciferous phytoalexin studies have been reported so far, but most of their absolute stereochemistry is still to be investigated. So we applied the VCD spectroscopy to determine the absolute configuration of dioxibrassinin (1) and 3-cyanomethyl-3-hydroxyoxindole (2). Compounds 1 and 2 were synthesized and their VCD spectra were measured. The comparison of observed VCD spectra and calculated ones indicated that their stereochemistry are both S. This is the first case of the determination of absolute stereochemistry of chiral tertiary alcohols by VCD. Application of VCD to carbohydrates Recently, the biological significance of carbohydrates have been recognized and analytical studies of carbohydrates have been widely investigated. Most analyses have been based on achiral methods such as NMR or MS in spite of their chiral properties. We considered that the detailed stereochemical information could be extracted using VCD. Various carbohydrates have been measured to construct an extensive database aiming to create a methodology for VCD pattern discrimination of the carbohydrates. The database in the fingerprint region indicated that sugars with the axial glycosidic linkage showed a negative, sharp and intense VCD band, named "Glycoside band" at around 1145 cm^<-1>. The applicability of the Glycoside band was demonstrated by quantifying α-β ratio of mixture samples and monitoring of an enzymatic reaction. In the C-H stretching region, we found the stereochemistry of single chiral center in the presence of multiple such centers could be extracted through the vibrational chirality transfer phenomenon. Also, VCD in this region was indicated to be a sensitive probe of glycosidic linkage sites. In conclusion, by using the VCD database and the proposed spectra-structure correlations, VCD will be an effective tool in carbohydrate analysis.
  • Miura Nobuaki, Taniguchi Tohru, Monde Kenji, Nishimura Shin-Ichiro  Abstracts of Symposium on Physical Organic Chemistry  17-  (0)  51  -51  2004  [Not refereed][Not invited]
     
    糖鎖は不斉炭素の集合体であり、その配座解析の確固たる方法論が未だにない。我々は配座解析の強力なツールとして分子軌道法を用い、不斉性を検出可能な振動領域円二色性スペクトルを計算することによって、測定されたスペクトルを再現することによって糖鎖の配座を混合比のレベルでの解析を行う。
  • M Hato, H Nakagawa, Y Takegawa, K Deguchi, K Monde, N Iwasaki, A Minami, H Kondo, SI Nishimura  GLYCOBIOLOGY  13-  (11)  870  -870  2003/11  [Not refereed][Not invited]
  • Y Takegawa, S Ito, S Yoshioka, K Deguchi, H Nakagawa, K Monde, SI Nishimura  GLYCOBIOLOGY  13-  (11)  844  -845  2003/11  [Not refereed][Not invited]
  • R Uematsu, H Nakagawa, K Deguchi, M Ota, K Yokota, H Shimizu, K Monde, SI Nishimura  GLYCOBIOLOGY  13-  (11)  846  -846  2003/11  [Not refereed][Not invited]
  • SI Nishimura, K Niikura, N Nagahori, R Uematsu, H Nakagawa, S Abe, H Moriyama, R Sadamoto, K Deguchi, K Monde, H Kondo  GLYCOBIOLOGY  13-  (11)  843  -844  2003/11  [Not refereed][Not invited]
  • 立花裕樹, 五十嵐幸太, 藤谷直樹, 津田栄, 門出健次, 西村紳一郎  高分子学会予稿集  52-  (13)  3755  -3756  2003/09/10  [Not refereed][Not invited]
  • 太田尚志, 藤谷直樹, 三浦信明, 新倉謙一, 鈴木隆, 鈴木康夫, 門出健次, 西村紳一郎  高分子学会予稿集  52-  (13)  3789  -3790  2003/09/10  [Not refereed][Not invited]
  • N Nagahori, R Sadamoto, K Niikura, K Monde, SI Nishimura  ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY  226-  U200  -U200  2003/09  [Not refereed][Not invited]
  • K Monde, T Taniguchi, N Miura, SI Nishimura  ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY  226-  U213  -U213  2003/09  [Not refereed][Not invited]
  • 太田尚志, 藤谷直樹, 三浦信明, 新倉謙一, 鈴木隆, 鈴木康夫, 門出健次, 西村紳一郎  日本化学会北海道支部研究発表会講演要旨集  2003-  56  2003/07/01  [Not refereed][Not invited]
  • Tachibana Yuki, Igarashi Kota, Monde Kenji, Nishimura Shin-Ichiro, Tsuda Sakae  Symposium on the Chemistry of Natural Products, symposium papers  44-  (0)  121  -126  2002  [Not refereed][Not invited]
     
    Antifreeze glycoproteins [AFGPs: {Ala-Thr(Galβ1-3GalNAcα)-Ala}_n, n=4-50] in the serum of polar fishes have been known to depress the freezing point of their blood and help them to survive at the temperature below-1.9℃[1]. Though it is widely accepted that AFGPs bind to the ice surface and prevent its growth, the definitive molecular mechanism of the action has not been solved yet. In this study, structure-activity relationships in AFGPs were studied toward understanding of the mechanism, thorough chemical syntheses, activity evaluations, and conformational analyses of the AFGP and its analogues, in which sugar or peptide moieties were different from those of the wild-type AFGP. The AFGP (1) and its analogues (2-8) were successfully synthesized via simple polymerization of their repeating unit using a DPPA method without any protection of sugar -OH groups [2]. Additionally, sialyl T-bearing glycopolypeptide (9) was successfully prepared through enzymatic elongation of a sialic acid residue to C-3 position of the galactose residue in the AFGP (1), indicating the broad applicability of this methodology for the syntheses of various glycopeptide polymers. In the evaluation assay of the antifreeze activity, artificial AFGP (1) showed similar activity as that of the wild-type AFGP. On the contrary, neither an AFGP repeating unit glycopeptide (19) nor a sugar-lacked polypeptide (poly-ATA, 8) shows the activity. Interestingly, AFGP analogs having GalNAc (2) or LacNAc (3) as sugar moiety showed similar activities as AFGP, while that of Galactose (4), Lactose (5), β-O-linked (6), and ASA (7) did not. These results clearly indicate the importance of i) repeating structure of glycopeptide, ii) NHAc group at C-2 position of the sugar moiety directly attached to the peptide, iii) α-glycosidic linkage between the sugar and the threonyl residue, for the specific interaction with ice. Furthermore, secondary structural analyses of the synthetic compounds were carried out by means of a CD spectroscopic method, in order to clarify the relationships between their conformations and their activities. The CD spectra of active compounds (1-3) were obviously different from those of inactive analogues (4-8), suggesting the presence of an ordered structure, but not α-helix.
  • K MONDE, M TAKASUGI  JOURNAL OF PESTICIDE SCIENCE  20-  (3)  339  -343  1995  [Not refereed][Not invited]
  • K MONDE, K TAMURA, M TAKASUGI, K KOBAYASHI, M SOMEI  HETEROCYCLES  38-  (2)  263  -267  1994/02  [Not refereed][Not invited]
     
    Isolation, structure elucidation, and synthesis of dehydro-4-methoxycyclobrassinin (1), a turnip phytoalexin possessing a novel heterocyclic system, are described.
  • MONDE Kenji  化学と工業 = Chemistry and chemical industry  45-  (2)  295  -299  1992/02/01

Books etc

  • 床波 志保, 前田 耕治, 安川 智之 (Contributor10章 旋光度と円偏光二色法（CD）)
    化学同人 2020/10 (ISBN: 9784759820225) vii, 177p 140-153
  • 化学便覧 基礎編 改訂6版
    日本化学会 (Contributor15章 分光学的性質 ―生体物質の円二色性―)
    丸善出版㈱ 2020 (ISBN: 9784621097243) 97-98
  • セラミド研究の新展開 ～基礎から応用へ～
    セラミド研究会 (Contributor第33章 ”天然物を利用したセラミド関連物質の化学合成戦略”)
    食品化学新聞社 2019 (ISBN: 9784916143358) 337 278-285
  • 日本化学会 (ContributorChap 2 ”赤外円二色スペクトルによる絶対配置決定”)
    化学同人 2013 (ISBN: 9784759813739) 43-49
  • 「赤外円二色性スペクトル法における新展開」
    門出 健次 
    高分子 2012 779-780
  • Berova Nina 
    John Wiley & Sons 2011 (ISBN: 9780470641354)
  • 高分子学会 
    共立出版 2007 (ISBN: 9784320043794)
  • 「第五版実験化学講座,１４巻, 有機化合物の合成（Ⅱ）」
    丸善株式会社 2005
  • Taylor Maureen, Drickamer Kurt 著, 西村 紳一郎, 門出 健次 
    化学同人 2005 (ISBN: 9784759810356)
  • 「植物病害の化学」
    学会出版センター 1997
  • 「２４章第３節第４項 絶対立体配置」, 有機合成実験法ハンドブック 第２版
    門出 健次 
    丸善出版

Association Memberships

  • The Japanese Conference on the Chemistiry of Lipids   THE CHEMICAL SOCIETY OF JAPAN   American Chemical Society   THE SOCIETY OF POLYMER SCIENCE, JAPAN   THE SOCIETY OF SYNTHETIC ORGANIC CHEMISTRY, JAPAN   Japanese Society for Ceramides   THE JAPANESE SOCIETY OF CARBOHYDRATE RESEARCH   フルオラス科学研究会   JAPAN OIL CHEMISTS' SOCIETY   JAPANESE SOCIETY FOR CHEMICAL BIOLOGY   

Research Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2025/03 
    Author : 岡崎 俊朗, 村井 勇太, 谷口 真, 門出 健次
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2019/04 -2023/03 
    Author : 門出 健次, 谷口 透, 村井 勇太
     
    赤外円二色性スペクトル（VCD）は、キラルな分子の立体構造を解析する分光法である。我々は「VCD励起子キラリティー」と命名した理論計算を必要としない最初の非経験的法則を見出している。本法はカルボニル基の二つの発色団の相互作用を基盤としており、極めて高感度である。本研究では、VCD励起子キラリティー法を１）アルキン、アジド、ニトリルなどの他のIR官能基に関しても適用可能であるか検証すること。２）本法を生体関連中分子等の立体構造解析へ適用すること。３）赤外円二色性スペクトル（VCD）と同様な振動分光であるキラルラマンスペクトル（ROA）での本法の展開性を検証することを目的としている。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
    Date (from‐to) : 2020/04 -2022/03 
    Author : 門出 健次
     
    現在、我が国の死亡原因はガンに続き、心疾患、脳血管疾患が上位を占める。その要因は主として脂質代謝疾患による脂質蓄積の異常が原因であると考えられている。脂質合成酵素の内、スフィンゴミエリン合成酵素(SMS)は、その阻害により、ガン免疫亢進、アミロイドβのクリアランス等に効果があることが知られている。我々は、フルーツより得られたマラバリコーンが高いSMS阻害能及び肥満抑制効果を有することを見出している。しかし、マラバリコーンによる肥満抑制効果についての詳細な分子機構は明らかとなっていない。本研究では、この分子機構を明らかにすることにより、ガン、肥満抑制に関する機構の情報を得ること目的としている。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Challenging Research (Exploratory)
    Date (from‐to) : 2017/06 -2020/03 
    Author : Monde Kenji
     
    L-serine, the head part of a sphingosine, is incorporated by serine palmitoyl transferase (SPT）, coupled with a palmitoyl CoA in the first stage of its biosynthesis and converted into ceramides. Recently, it has been suggested that not only L-serine but also other amino acids may be incorporated into this biosynthetic system, and its association with lipid-related diseases has been trend. We have been succeeded in synthesizing sphingosines having phenylalanine, alanine, tryptophan, leucine, cysteine, and threonine in its head part for the purpose of providing authentic standard samples in a mass spectrometric analysis. We also constructed a unique ceramide library by binding some of these to fatty acids. It was found that some of them showed inhibitory activity of sphingomyelin synthase.
  • ポリエステル系ペプチドミミックを指向したVCDによるバイオポリマー立体構造解析法
    文部科学省科学研究費：基盤研究(B)
    Date (from‐to) : 2015/04 -2018/03 
    Author : 門出 健次
  • 理論計算を必要としない赤外円二色性スペクトルによる新規絶対配置決定法の開発
    文部科学省科学研究費：基盤研究(B)
    Date (from‐to) : 2012/04 -2015/03 
    Author : 門出 健次
  • 先端融合領域イノベーション創出拠点の形成
    科学技術振興機構（文部科学省）：未来創薬・医薬イノベーション拠点形成
    Date (from‐to) : 2006 -2015 
    Author : 山口 佳三
  • フードイノベーション創造支援事業（札幌市補助事業）
    札幌市：実証研究支援補助金
    Date (from‐to) : 2014 
    Author : 門出 健次
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2011 -2013 
    Author : 門出 健次, CHANNAPILLE Kopp
     
    本研究では、特別研究員のこれまでの合成技術により合成した化合物を合成し、立体化学研究をVCD法により遂行、新規キラルドラッグライク化合物ライブラリの構築することを目的としている。本年度は生理活性物質として、スフィンゴシンにしぼった。スフィンゴシンは、疎水性、親水性の両方性質をもつため取扱いが困難である。そのため、昨年に引き続きスフィンゴシン補足樹脂の合成と最適化を実施した。スフィンゴシン補足樹脂作成のため、グルタルアルデヒド誘導体の大量合成を実施した。また、樹脂に関しても複数種類を入手し、カップリングにより補足樹脂の最適化を試みたが、当面、従来法の樹脂が最適であるとの結論を得た。また、ファイトスフィンゴシンに対しても補足、リリースの最適化を行った。樹脂は、ファイトスフィンゴシン類に関しても有効であることが判明した。更に、多様性化合物の確保をめざして、天然資源からの簡便抽出法の開発を試みた。サンプルとして、タモギダケを選び、これからグルコセラミドを大量に単離、標準サンプルとした。糖鎖の加水分解を実施したが、反応の進行が困難であったので、詳細な加水分解の条件検討を実施した。また、別途合成されたスフィンゴシン誘導体を用いて、2位のアミノ基に対して、研究室保有のカルボン酸ライブラリのアミド化反応による多種類化合物の調整を試みた。特に、多種類のカルボン酸に対して、容易かつ確実に進行する条件を検討した。また、合成した光学活性生理活性物質に関して、単離することなく、プレート上での生理活性試験を実施した。脂質関係酵素を含む細胞系と蛍光ラベル基質を用いたアッセイ系での活性測定を試みた。その結果、一部について活性が認められた。
  • 官能基特異的反応に着目したスフィンゴシン類の選択的捕捉法の開発
    文部科学省科学研究費：挑戦的萌芽研究
    Date (from‐to) : 2011 -2013 
    Author : 門出 健次
  • 赤外円二色性スペクトルによる分子キラル分析法の開発
    財団法人篷庵社：研究助成金
    Date (from‐to) : 2010 -2013 
    Author : 門出 健次
  • さっぽろバイオクラスター構想 ”Bio-S”
    文部科学省：知的クラスター創成事業（第II期）
    Date (from‐to) : 2007 -2011 
    Author : 鈴木 文夫
  • 赤外円二色法によるスタンダード・キロプティカル構造解析法の構築
    文部科学省科学研究費：基盤研究(B)
    Date (from‐to) : 2008 -2010 
    Author : 門出 健次
  • 生物によるキラル円偏光識別とその分子機構の解明
    文部科学省科学研究費：挑戦的萌芽研究
    Date (from‐to) : 2008 -2010 
    Author : 門出 健次
  • 疾患早期診断のための糖鎖自動分析装置開発
    科学技術振興機構（文部科学省）：先端計測分析技術機器・開発事業
    Date (from‐to) : 2004 -2008 
    Author : 西村 紳一郎
  • 弱い相互作用に着目した機能性天然物の高速探索
    文部科学省科学研究費：萌芽研究
    Date (from‐to) : 2005 -2007 
    Author : 門出 健次
  • 赤外領域円二色性スペクトルによるキラル分析法の応用研究
    文部科学省科学研究費：基盤研究(B)
    Date (from‐to) : 2004 -2007 
    Author : 門出 健次
  • 不凍糖タンパク質の生理機能を活用する臓器・細胞保存剤の開発
    経済産業省：地域コンソーシアム研究開発事業
    Date (from‐to) : 2004 -2005 
    Author : 西村 紳一郎
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2003 -2005 
    Author : JIN Takashi, MONDE Kenji
     
    Lipid bilayer membranes that respond to light are of great interest for the development of the artificial visual systems for use in optoelectronic devices and optical transducers. There are many studies of the photocontrol of ion transport across lipid bilayer membranes using photoresponsive compounds such as amphiphilic azobenzene and spirobenzopyran derivatives. Most of the studies have used changes in membrane capacitance due to the disruption of lipid bilayer structures, which results from the photoisomerization of the compounds incorporated into the lipid bilayers. So far, several groups have reported photocontrollable ion transport systems, where channel or carrier molecules attaching photochromic compounds were incorporated into lipid bilayer membranes. In these systems, photochromic reaction has been conducted by irradiation of UV light (300-380nm). The prolonged UV irradiation, however, usually results in photodamage to photochromic compounds and lipid molecules. In the present study, we have chosen calix[4]arene as a basic skeleton of a photoresponsive ion carrier because its ether derivatives are known to act as Na^+ ion carriers in lipid bilayer membranes. For the synthesis of a photoresponsive carrier, dimethylaminoazobenzene was introduced as a photochromic compound to an ether derivative of p-tert-butylcalix[4]arene. Among azobenzene derivatives, dimethylaminoazobenzene has an intense absorption in the visible region, which is attributed to the π-π* transition of the trans isomer. We expected that the dimethylaminoazobenzene appended calix[4]arene derivative mediates Na^+ ion transport across a lipid bilayer membrane, and the ion transport ability can be controlled by irradiation of visible light. In this study, we have succeeded to develop a visible light-driven ion transport system using a calix[4]arene-based photoresponsive ion carrier, where Na^+ flux across a lipid bilayer can be controlled by irradiation of light (>400nm).
  • 糖鎖自動合成装置における反応モニタリング技術の開発
    経済産業省：糖鎖エンジニアリングプロジェクト/糖鎖構造解析技術開発
    Date (from‐to) : 2003 -2005 
    Author : 西村 紳一郎
  • 人工細胞外マトリックスの精密分子設計と靭帯および関節軟骨細胞再生への応用
    文部科学省科学研究費：基盤研究(B)
    Date (from‐to) : 2003 -2005 
    Author : 眞島 任史
  • 複合糖鎖データベースリーディングプロジェクト
    文部科学省：新世紀重点研究創成プラン（ＲＲ）
    Date (from‐to) : 2003 -2004 
    Author : 西村 紳一郎
  • 複合糖質の新規キラル分析法の開発
    文部科学省科学研究費：萌芽研究
    Date (from‐to) : 2002 -2004 
    Author : 門出 健次
  • 北方系植物資源データベースの構築及び抽出物ライブラリの整備
    国土交通省：一次産品活用型バイオベンチャー育成支援調査
    Date (from‐to) : 2004 
    Author : 門出 健次
  • 機能性糖鎖複合材料創製技術開発
    経済産業省：大学連携産業科学技術研究開発プロジェクト
    Date (from‐to) : 1999 -2003 
    Author : 西村 紳一郎
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 1999 -2002 
    Author : HARADA Nobuyuki, MATSUMOTO Takatoshi, WATANABE Masataka
     
    1. We have developed a new strategy for determining the absolute configuration of mono-fucntional compounds by the CD exciton chirality method. This method is powerful for the absolute configurational studies of chiral compounds including natural products. 2. We have recently developed two "powerful chiral acids" for enantioresolution of various alcohols by HPLC on silica gel and also for determination of their absolute configurations by X-ray crystallography and/or by the 1H NMR anisotropy method. The first is the chiral dichlorophthalic acid (-)-1, which was reacted with racemic alcohol to give a diastereomeric mixture of esters. The mixture of esters obtained was separated by HPLC on silica gel, and two separated esters were crystallized respectively to afford single crystals suitable for X-ray analysis. The absolute configuration of the alcohol part was determined by X-ray crystallography of the esters, and enantiopure alcohols were easily recovered by solvolysis with K_2CO_3 in methanol. 3. The second powerful chiral acid is 2-methoxy-2-(1-naphthyl)propionic acid (MαNP acid, (S)-(+)-2 or R-(-)-2) for determining the absolute configuration of chiral alcohols by the 1H NMR anisotropy method.The enantiopure MαNP acid (S)-(+)-2 was allowed to react with racemic alcohols yielding diastereomeric mixtures of esters, which were easily separated by HPLC on silica gel. The NMR signals of diastereomeric esters obtained were fully assigned by the various two-dimensional methods leading to the calculation of Δδ values (Δδ = δ(R,X)-δ(S,X)). By applying the MαNP sector rule, the absolute configuration X was determined. Separated esters were hydrolyzed with KOH/EtOH to recover enantiopure alcohols. 4. Using MαNP acid, (S)-(+)-2 and its deuterium labeled enantiomer R-(-)-2-d_6, we have developed a new diastereomer method for determining enantiomeric excess (% ee) of chiral alcohols by MS spectrometry.
  • コンピュータを用いた生物有機資源からの消化抑制剤等の開発
    経済産業省：即効型地域新生コンソーシアム研究開発事業
    Date (from‐to) : 2002 
    Author : 門出 健次
  • 色覚に関与する視物質のモデル化合物による解析
    文部科学省科学研究費：奨励研究(A)
    Date (from‐to) : 1999 -2000 
    Author : 門出 健次
  • Pacifichem2000渡航費用
    栗林育英学術財団：
    Date (from‐to) : 2000 
    Author : 門出 健次
  • フッ素ラベルリガンドとレセプターとの相互作用に関する研究
    文部省・科学研究費：奨励研究(A)
    Date (from‐to) : 1997 -1998 
    Author : 門出 健次
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 1994 -1994 
    Author : 高杉 光雄, 門出 健次
     
    1.アブラナ科植物のファイトアレキシンの産生を誘導する内因性エリシターの探索 カブを大根おろし状とし、おろし汁を除去、洗浄したカブ繊維状組織を滅菌水に懸濁し、紫外線を照射した後、水層に滲出してくる物質にエリシター活性を認めた。透析により分子量約1000以上の不活性部を除き、ファイトアレキシンcyclobrassininの生成量をエリシター活性の指標として各種クロマトグラフィーにより分離し、酸性糖質分画に活性を認めた。 2.cyclobrassinin生合成経路の検討 cyclobrassininがmethoxybrassininを経由するか、あるいはbrassininから直接生成するか検討した。重水素標識brassininを投与した後、単離したcyclobrassininとmethoxybrassininについて重水素標識の取り込を調査したところ、cyclobrassininには取り込まれたもののmethoxybrassininには全く取り込まれていなかった。また重水素標識methoxybrassininの投与により得たcyclobrassininにも重水素標識が全く取り込まれないことも確認した。従って、cyclobrassininはmethoxybrassininを経由しないで生合成される。 3.brassicanal Aの生合成研究 紫外線照射により活性化したカブスライスに、生体異物であるアセトアニリドを投与したところ、アセトアニリド由来のアニリンがbrassicanal Aの生合成中間体をトラップした構造の生成物を得た。これより、cyclobrassininより生成するdehydrobrassininの加水分解生成物、3-formyl-2-mercaptoindoleのメチル化によりbrassicanal Aが生合成されると推定した。
  • シロイヌナズナのファイトアレキシン及びその生合成研究
    文部省・科学研究費：奨励研究(A)
    Date (from‐to) : 1993 
    Author : 門出 健次
  • 18th IUPAC International Symposium on the Chemistry of Natural Products渡航費用
    実吉財団：
    Date (from‐to) : 1992 
    Author : 門出 健次
  • アブラナ科植物ファイトアレキシンの生合成研究
    文部省・科学研究費：奨励研究(A)
    Date (from‐to) : 1992 
    Author : 門出 健次
  • アブラナ科植物の産生する新規含硫ファイトアレキシンの生物有機化学的研究
    文部省・科学研究費：一般研究(B)
    Date (from‐to) : 1988 -1990 
    Author : 高杉 光雄
  • 電荷移動プロセスとひずみ結合の反応性
    文部省・科学研究費：一般研究(C)
    Date (from‐to) : 1990 
    Author : 平尾 健一
  • ヒラタケ病原菌の生理活性物質に関する研究
    北海道大学：教育研究学内特別経費
    Date (from‐to) : 1990 
    Author : 門出 健次
  • ヒラタケ病原細菌の生産する生理活性物質に関する生物有機化学的研究
    秋山記念生命科学振興財団：
    Date (from‐to) : 1990 
    Author : 門出 健次
  • 17th IUPAC International Symposium on the Chemistry of Natural Products渡航費用
    薬学振興財団：
    Date (from‐to) : 1990 
    Author : 門出 健次
  • 細菌感染により誘導されるキク科食用植物の抗菌活性物質の生物有機化学的研究
    文部省・科学研究費：奨励研究(A)
    Date (from‐to) : 1989 
    Author : 門出 健次
  • Chiral analysis of glycoconjugates by Vibrational Circular Dichroism (VCD)

Industrial Property Rights

  • 特願2021-102280:抗ウイルス剤  2021年/06/21
    門出 健次, 村井 勇太, 五十嵐 靖之, 臼杵 靖剛, 澤 洋文, 大場 靖子, 佐々木 道仁  国立大学法人北海道大学
  • 特願2021-041717:化合物、その製造方法、複合体および短波赤外蛍光剤  2021年/03/15
    神 隆, マカナハリ マデゴウダ マハデバ スワミィ, 門出 健次, 村井 勇太  国立研究開発法人理化学研究所, 国立大学法人北海道大学
  • 特願2020-117350:トリグリセリドの代謝能に関する値の取得方法、疾患の情報の提示方法、疾患の鑑別情報の提示方法、治療の有効性情報の提示方法、検査試薬、及び検査キット  2020年/07/07
    平野 賢一, 原 康洋, 柏木 浩和, 鈴木 朗, 神 隆, 門出 健次, 村井 勇太  国立大学法人大阪大学, 国立研究開発法人理化学研究所, 国立大学法人北海道大学
  • 特開2019-104692:スフィンゴミエリン合成酵素阻害剤  2019/06/27
    門出 健次, 村井 勇太, マカナハリ マデゴウダ マハデバ スワミィ  国立大学法人北海道大学
  • 特開2019-104691:スフィンゴミエリン合成酵素阻害剤  2019/06/27
    門出 健次, 村井 勇太, マカナハリ マデゴウダ マハデバ スワミィ  国立大学法人北海道大学
  • 門出 健次, ハンマン モスタファ アハメド サベット アハメド, 須賀 好子, 吉田 裕, 松村 謙一  塩野義製薬株式会社, 国立大学法人北海道大学  201703000395148174
  • 門出 健次, 五十嵐 靖之, 臼杵 靖剛, ボメゴウダ シッダバサーブ ゴウダ  国立大学法人北海道大学  201603017183529154
  • 門出 健次, 山口 淳二, 深澤 知行  国立大学法人 北海道大学, 日本分光株式会社  201403039448597376
  • 特開2008-189705:撥水性および撥油性表面を有する物品およびその製造法  2008/08/21
    辻井 薫, 黒木一誠, 門出健次  国立大学法人 北海道大学
  • 特開2005-306836:α-アミラーゼ阻害剤  2005/11/04
    門出 健次, 西村 紳一郎, 内田 直人, 三浦 信明, 森山 英樹, 前川 宣彦  株式会社生物有機化学研究所
  • 特開2005-69998:VCDを利用した糖の分析法  2005/03/17
    門出 健次, 谷口 透, 三浦 信明, 西村 紳一郎  塩野義製薬株式会社
  • 特願2003-27690:糖ペプチドおよびそのプロテオグリカンイニシエーターとしての使用  2003年/02/04
    西村 紳一郎, 佐藤 史洋, 門出 健次  西村 紳一郎

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