Researcher Database
Last Updated :2024/09/03
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Profile and Settings
Degree
Profile and Settings
Name (Japanese)
MAKOTOName (Kana)
HashimotoName
200901044353767432
Alternate Names
Achievement
Research Interests
- ジアジリン 機能部位解析 構造活性相関 安定同位体 質量分析 アビジンービオチン 結合部位解析 異性化 固層担体 抗体-抗原反応 有機化学反応 有機反応 セラミダーゼ 核酸-蛋白質相互作用 糖脂質 脂肪酸 アビジン-ビオチン系 薬学 医薬分子機能学 生体機能利用 分子認識 生体分子 光アフィニティーラベル Photoaffinity labeling
Research Areas
- Nanotechnology/Materials / Biochemistry
- Nanotechnology/Materials / Chemical biology
- Nanotechnology/Materials / Synthetic organic chemistry
- Life sciences / Food sciences
- Life sciences / Bioorganic chemistry
- Nanotechnology/Materials / Molecular biochemistry
Research Experience
- 2021 - Today Hokkaido University
- 2010 - 2020 Hokkaido University
- 2003 - 2009 Obihiro University of Agriculture and Veterinary Medicine
- 1997 - 2003 Obihiro University of Agriculture and Veterinary Medicine
- 1995 - 1997 富山医科薬科大学 日本学術振興会特別研究員
Education
- - 1997 Hokkaido University
- - 1997 Hokkaido University Graduate School, Division of Pharmaceutical Sciences
- - 1989 Hokkaido University Faculty of Pharmaceutical Sciences
- - 1989 Hokkaido University Faculty of Pharmaceutical Science
Awards
Published Papers
- Zetryana Puteri Tachrim, Makoto HashimotoCurrent Organic Chemistry 28 (16) 1225 - 1228 1385-2728 2024/09 [Refereed][Invited]
: The Friedel-Crafts acylation of natural or unnatural amino acids in stereoretardedmanner is willing to prescribed here. Depending on its main skeleton, the typicalintra- and intermolecular Friedel-Crafts reaction of amino acids can be differentiated. Theunique amino acid’s general structure can contribute to the reaction between its carboxylgroup and the side chain. Depending on the Friedel-Crafts reaction condition, the aminoacid’s optical retention can be retarded. This perspective can contribute to the developmentof this one-century reaction in the field of organic chemistry. - Rose Malina Annuur, Desita Triana, Teni Ernawati, Yuta Murai, Muhammad Aswad, Makoto Hashimoto, Zetryana Puteri TachrimMolecules 29 (16) 3929 - 3929 2024/08/20 [Refereed]
Antimicrobial resistance has emerged as a significant danger to global health, and the need for more effective antimicrobial resistance (AMR) control has been highlighted. Cinnamic acid is abundant in plant products and is a potential starting material for further modification, focusing on the development of new antimicrobial compounds. In the following review, we describe the classification of critical antibacterial-guided reactions applied to the main skeleton structure of cinnamic acid derivatives over the last decade. Of all of the main parts of cinnamic acids, the phenyl ring and the carboxylic group significantly affect antibacterial activity. The results presented in the following review can provide valuable insights into considerable features in the organic modification of cinnamic acids related to antibacterial medication development and the food industry. - Wen Zhang, Kazu Sunami, Shuo Liu, Zihan Zhuang, Yasuko Sakihama, Da-Yang Zhou, Takeyuki Suzuki, Yuta Murai, Makoto Hashimoto, Yasuyuki HashidokoBioscience, Biotechnology, and Biochemistry 2023/08/01 [Refereed][Not invited]
Abstract Squalene is a triterpenoid compound and widely used in various industries such as medicine and cosmetics due to its strong antioxidant and anticancer properties. The purpose of this study is to increase the accumulation of squalene in filamentous fungi using exogeneous butenafine hydrochloride, which is an inhibitor for squalene epoxidase. The detailed settings achieved that the filamentous fungi, Trichoderma virens PS1-7, produced squalene up to 429.93 ± 51.60 mg/L after culturing for 7 days in the medium consisted of potato infusion with glucose at pH 4.0, in the presence of 200 μM butenafine. On the other hand, no squalene accumulation was observed without butenafine. This result indicated that squalene was biosynthesized in the filamentous fungi PS1-7 which can be used as a novel source of squalene. In addition, we successfully obtained highly 13C-enriched squalene by using [U-13C6]-glucose as a carbon source replacing normal glucose. - Zetryana Puteri Tachrim, Manami Hashinoki, Zeping Wang, Zhang Wen, Zhuang Zihan, Makoto HashimotoJournal of Labelled Compounds and Radiopharmaceuticals 0362-4803 2023/06/19 [Refereed]
- Yuta Murai, Makoto HashimotoMolecules (Basel, Switzerland) 28 (3) 2023/02/01 [Refereed]
In materials (polymer) science and medicinal chemistry, heteroaromatic derivatives play the role of the central skeleton in development of novel devices and discovery of new drugs. On the other hand, (3-trifluoromethyl)phenyldiazirine (TPD) is a crucial chemical method for understanding biological processes such as ligand-receptor, nucleic acid-protein, lipid-protein, and protein-protein interactions. In particular, use of TPD has increased in recent materials science to create novel electric and polymer devices with comparative ease and reduced costs. Therefore, a combination of heteroaromatics and (3-trifluoromethyl)diazirine is a promising option for creating better materials and elucidating the unknown mechanisms of action of bioactive heteroaromatic compounds. In this review, a comprehensive synthesis of (3-trifluoromethyl)diazirine-substituted heteroaromatics is described. - Hitoshi Wakabayashi, Koji Sugiyama, Shinichi Suzuki, Yasuko Sakihama, Makoto Hashimoto, Martin J. BarwoodEuropean Journal of Applied Physiology 1439-6319 2022/10/28 [Refereed]
- Additive-free aerobic oxidation of hydroazobenzenes: Access to azobenzenes and epoxidation of enonesYu Lin, Hao Wu, Ziang Liu, Jin Li, Rui Cai, Makoto Hashimoto, Lei WangTetrahedron Letters 108 154132 - 154132 0040-4039 2022/10 [Refereed]
- Hydrogen-deuterium exchange of indole-3-propionic acid with deuterated trifluoromethanesulfonic acidWen Zhang, Zetryana Puteri Tachrim, Yurika Tokoro, Zeping Wang, Shoko Ishikawa, Yuta Murai, Takeyuki Suzuki, Makoto HashimotoArkivoc 2022 (9) 33 - 39 2022/08/31 [Refereed][Not invited]
- Zeping Wang, Shoko Ishikawa, Fumina Ohashi, Reo Sagisaka, Yuta Murai, Zetryana Puteri Tachrim, Takeyuki Suzuki, Makoto HashimotoHETEROCYCLES 105 (1) 406 - 416 0385-5414 2022 [Refereed]
- Yuta Murai, Takuma Yoshida, Zetryana Puteri Tachrim, Makoto HashimotoHETEROCYCLES 104 (1) 167 - 167 0385-5414 2022 [Refereed]
- Makoto Hashimoto, Tomoya Nakagita, Takumi MisakaRSC Advances 11 (51) 32236 - 32247 2021/10 [Refereed][Invited]
The review summarized recent progress for the elucidation of the chemoreception mechanism of sweet taste receptor–sweetener interactions with photoaffinity labeling. - Zetryana Puteri Tachrim, Lei Wang, Yuta Murai, Makoto HashimotoMolecules 26 (15) 4496 - 4496 2021/07/26 [Refereed]
This review focuses on diaziridine, a high strained three-membered heterocycle with two nitrogen atoms that plays an important role as one of the most important precursors of diazirine photoaffinity probes, as well as their formation and transformation. Recent research trends can be grouped into three categories, based on whether they have examined non-substituted, N-monosubstituted, or N,N-disubstituted diaziridines. The discussion expands on the conventional methods for recent applications, the current spread of studies, and the unconventional synthesis approaches arising over the last decade of publications. - Makoto HashimotoBioscience, Biotechnology, and Biochemistry 85 (1) 194 - 195 2021/01/07 [Refereed][Invited]
- Masataka Hane, Hanny C Wijaya, Yanetri A Nyon, Yasuko Sakihama, Makoto Hashimoto, Hideyuki Matsuura, Yasuyuki HashidokoBioscience, Biotechnology, and Biochemistry 85 (1) 77 - 84 0916-8451 2021/01/07 [Refereed]
Abstract Symbiosis of Penicillium rolfsii Y-1 is essential for the seed germination of Hawaii yellow-eyed grass (Xyris complanata). However, the local soil where the plants grow naturally often suppresses the radicle growth of the seedlings. This radicle growth was drastically restored by coinoculation of Paraburkholderia phenazinium isolate CK-PC1, which is a rhizobacterium of X. complanata. It was found that the isolate CK-PC1 produced phenazine-1-carboxylic acid (PCA, 1) as a major metabolite. The biological effects of PCA (1) were investigated using the seeds of X. complanata and Mung bean (Vigna radiata) and it was uncovered that the symbiosis of the isolate CK-PC1was essential for the postgermination growth of X. complanata and the metabolite PCA (1) might partially contribute to promote the growth of the plants. - Manami Hashinoki, Natsumi Kurokawa, Yuta Murai, Zetryana Puteri Tachrim, Yasuko Sakihama, Takeyuki Suzuki, Makoto HashimotoHETEROCYCLES 103 (1) 392 - 392 0385-5414 2021 [Refereed]
- Zetryana Puteri Tachrim, Kazuhiro Oida, Fumina Ohashi, Natsumi Kurokawa, Lei Wang, Takeyuki Suzuki, Makoto HashimotoLetters in Organic Chemistry 17 (8) 645 - 653 1570-1786 2020/08/18 [Refereed]
α-Amino acid chlorides are reactive coupling agents in amide (peptide) formation. The Vilsmeier reagent ((chloromethylene)dimethylammonium chloride) offers a convenient way to prepare α-amino acid chlorides for peptide synthesis. Its use with N-trifluoracetyl (TFA)-protected isoleucine and allo-isoleucine is described. The 1H-NMR of the α-proton signal offers a convenient way to monitor the chirality retention in the acid chloride forming reaction and subsequent Friedel-Crafts acylation of arenes which result in α-amino acid aryl-ketone with no loss of chirality. - Tomoya Nakagita, Akiko Ishida, Zetryana Puteri Tachrim, Lei Wang, Takumi Misaka, Makoto HashimotoMolecules (Basel, Switzerland) 25 (12) 2020/06/17 [Refereed][Not invited]
Lactisole, which has a 2-phenoxy propionic acid skeleton, is well-known as an inhibitor of sweet taste receptors. We recently revealed some of the structure-activity relationships of the aromatic ring and chiral center of lactisole. Photoaffinity labeling is one of the common chemical biology methods to elucidate the interaction between bioactive compounds and biomolecules. In this paper, the novel asymmetric synthesis of lactisole derivatives with common photophores (benzophenone, azide and trifluoromethyldiazirine) for photoaffinity labeling is described. The synthetic compounds are subjected to cell-based sweet taste receptors, and the substitution with trifluoromethyldiazirinyl photophore shows the highest affinity to the receptor of the synthesized compounds. - Hydrogen-Deuterium Exchange of Histidine and Histamine with Deuterated Trifluoromethanesulfonic AcidZetryana Puteri Tachrim, Natsumi Kurokawa, Yurika Tokoro, Makoto HashimotoHETEROCYCLES 101 (1) 357 - 357 0385-5414 2020 [Refereed]
- Tachrim, Zetryana Puteri, Nakagawa, Shiori, Nakamura, Tadashi, Ohashi, Fumina, Kurokawa, Natsumi, Wakasa, Haruna, Tokoro, Yurika, Sakihama, Yasuko, Hashidoko, Yasuyuki, Suzuki, Takeyuki, Hashimoto, MakotoHETEROCYCLES 99 (1) 404 - 414 0385-5414 2019/04 [Refereed][Not invited]
CycloDOPA (5,6-dihydroxy-indoline-2-carboxylic acid, leukodopachrome) is one of metabolites derived from tyrosine, one of intermediate in melanin formation (mammalian) and betanidin main skeleton (betalain pigment in plant). Synthesis of deuterated cyclodopa via hydrogen/deuterium exchange by utilization of deuterium chloride (DCl) and deuterated triflic acid (TfOD) are reported. The novel fully deuterated aromatic cycloDOPA derivative can be formed depending on temperature and time of H/D exchange condition. The complete study of H/D exchange resulted in the selective deuterium between 4- and/or 7-position of aromatic hydrogen of cycloDOPA. - Yasuyuki Hashidoko, Hiroaki Nishizuka, Manato Tanaka, Kanako Murata, Yuta Murai, Makoto HashimotoScientific reports 9 (1) 4751 - 4751 2019/03/18 [Refereed][Not invited]
Coralloid roots are specialized tissues of cycads (Cycas revoluta) that are involved in symbioses with nitrogen-fixing Nostoc cyanobacteria. We found that a crude methanolic extract of coralloid roots induced differentiation of the filamentous cell aggregates of Nostoc species into motile hormogonia. Hence, the hormogonium-inducing factor (HIF) was chased using bioassay-based isolation, and the active principle was characterized as a mixture of diacylglycerols (DAGs), mainly composed of 1-palmitoyl-2-linoleoyl-sn-glycerol (1), 1-palmitoyl-2-oleoyl-sn-glycerol (2), 1-stearoyl-2-linolenoyl-sn-glycerol (3), and 1-stearoyl-2-linoleoyl-sn-glycerol (4). Enantioselectively synthesised compound 1 showed a clear HIF activity at 1 nmol (0.6 µg) disc-1 for the filamentous cells, whereas synthesised 2-linoleoyl-3-palmitoyl-sn-glycerol (1') and 1-palmitoyl-2-linoleoyl-rac-glycerol (1/1') were less active than 1. Conversely, synthesised 1-linoleoyl-2-palmitoyl-rac-glycerol (8/8') which is an acyl positional isomer of compound 1 was inactive. In addition, neither 1-monoacylglycerols nor phospholipids structurally related to 1 showed HIF-like activities. As DAGs are protein kinase C (PKC) activators, 12-O-tetradecanoylphorbol-13-acetate (12), urushiol C15:3-Δ10,13,16 (13), and a skin irritant anacardic acid C15:1-Δ8 (14) were also examined for HIF-like activities toward the Nostoc cells. Neither 12 nor 13 showed HIF-like activities, whereas 14 showed an HIF-like activity at 1 nmol/disc. These findings appear to indicate that some DAGs act as hormogonium-inducing signal molecules for filamentous Nostoc cyanobacteria. - Makoto HashimotoReference Module in Chemistry, Molecular Sciences and Chemical Engineering 2019 [Refereed][Invited]
- Tomoya Nakagita, Akiko Ishida, Takumi Matsuya, Takuya Kobayashi, Masataka Narukawa, Takatsugu Hirokawa, Makoto Hashimoto, Takumi MisakaPLoS ONE 14 (3) e0213552 2019 [Refereed][Not invited]
Lactisole, an inhibitor of the human sweet taste receptor, has a 2-phenoxypropionic acid skeleton and has been shown to interact with the transmembrane domain of the T1R3 subunit (T1R3-TMD) of the receptor. Another inhibitor, 2,4-DP, which shares the same molecular skeleton as lactisole, was confirmed to be approximately 10-fold more potent in its inhibitory activity than lactisole; however the structural basis of their inhibitory mechanisms against the receptor remains to be elucidated. Crystal structures of the TMD of metabotropic glutamate receptors, which along with T1Rs are categorized as class C G-protein coupled receptors, have recently been reported and made it possible to create an accurate structural model for T1R3-TMD. In this study, the detailed structural mechanism underlying sweet taste inhibition was characterized by comparing the action of lactisole on T1R3-TMD with that of 2,4-DP. We first performed a series of experiments using cultured cells expressing the sweet taste receptor with mutations and examined the interactions with these inhibitors. Based on the results, we next performed docking simulations and then applied molecular dynamics-based energy minimization. Our analyses clearly revealed that the (S)-isomers of both lactisole and 2,4-DP, interacted with the same seven residues in T1R3-TMD and that the inhibitory potencies of those inhibitors were mainly due to stabilizing interactions mediated via their carboxyl groups in the vertical dimension of the ligand pocket of T1R3-TMD. In addition, 2,4-DP engaged in a hydrophobic interaction mediated by its o-Cl group, and this interaction may be chiefly responsible for the higher inhibitory potency of 2,4-DP. - Kurokawa, Natsumi, Tokoro, Yurika, Tachrim, Zetryana Puteri, Wakasa, Haruna, Sakihama, Yasuko, Hashidoko, Yasuyuki, Hashimoto, MakotoARKIVOC (5) 42 - 49 1551-7004 2019 [Refereed][Not invited]
A chiral N-protected alpha-amino acid N-hydroxysuccinimide ester (OSu) is a common useful reagent for peptide bond formation. Recently, N-trifluoroacetyl (TFA) alpha-amino acid OSu esters have been reported as acyl donors for Frieldel-Crafts reactions to synthesize chiral alpha-amino phenyl ketones retaining the configurations of the starting alpha-amino acids. There are few reports for chiral TFA protected methionine, which has methylthioethyl structure in the side-chain of the alpha-amino acid. The detailed synthesis of chiral TFA-Met-OSu and its application as an acyl donor for Friedel-Crafts acylation is reported.[GRAPHICS]. - Tachrim, Zetryana Puteri, Oida, Kazuhiro, Ohashi, Fumina, Wakasa, Haruna, Ikemoto, Haruka, Kurokawa, Natsumi, Sakihama, Yasuko, Hashidoko, Yasuyuki, Suzuki, Takeyuki, Hashimoto, MakotoHETEROCYCLES 97 (2) 877 - 893 0385-5414 2018/09 [Refereed][Not invited]
The utilization of N-trifluoroacetyl (TFA)-alpha-amino acid N-hydroxysuccinimide ester (OSu) derivatives, a promising acylating agent with high storage stability, is reported for Friedel Crafts acylation into arenes and N-heterocycles. The reaction between TFA-Phe-OSu derivatives and arenes afforded inter- and intramolecular products. TFA-Tyr-OSu derivatives, which possess hydroxyl substituent in the aromatic moiety of phenylalanine, afforded only intermolecular product with benzene. The heterocyclic TFA-Pro-OSu also shows relatively high reactivity toward acylation. - Tachrim, Zetryana Puteri, Nakamura, Tadashi, Sakihama, Yasuko, Hashidoko, Yasuyuki, Hashimoto, MakotoARKIVOC (7) 341 - 348 1551-7004 2018 [Refereed][Not invited]
1-kestose (O-B-D-fructofuranosyl-(2 -> 1)-B-D-fructofuranosyl-(2 -> 1)-alpha-D-glucopyranoside) is a potential short chain fructooligosaccharide with an inulin-type skeleton. Halogenation of 1-kestose was conducted via the Appel reaction with the use of carbon tetrahalide (CBr4 or CCI4) and triphenylphosphine, which was then followed by conventional acetylation. The per-O-acetylated form of 6,6',6 ''-trihalogenated derivatives of 1-kestose were conveniently isolated. Further deprotection of the per-O-acetylated form resulted in 6-, 6'-, and 6 ''-trihalogenated derivatives. The structure elucidation by one- and two-dimensional nuclear magnetic resonance established that halogenations are specific at the 6-, 6'-, and 6 ''-position of 1-kestose primary alcohols.[GRAPHICS]. - Lei Wang, Zetryana Puteri Tachrim, Natsumi Kurokawa, Fumina Ohashi, Haruna Wakasa, Yasuko Sakihama, Yasuyuki Hashidoko, Takeyuki Suzuki, Makoto HashimotoARKIVOC (7) 58 - 65 1551-7004 2018 [Refereed][Not invited]
Sucrose is well known as naturally occurring sweeteners. Photoreactive sucrose derivative containing 3-(trifluoromethyl)diazirinyl moiety is designed for photoaffinity labeling. As 1'-hydroxyl group of sucrose is well known to be less reactive than other primary alcohols, the optimization of reaction conditions for diazirinyl benzyl bromide derivative at sucrose 1'-portion was examined to elucidate the functional analysis of sweet receptors.[GRAPHICS]. - Shiori Nakagawa, Zetryana Puteri Tachrim, Natsumi Kurokawa, Fumina Ohashi, Yasuko Sakihama, Takeyuki Suzuki, Yasuyuki Hashidoko, Makoto HashimotoMolecules 23 (8) 1943 2018 [Refereed][Not invited]
© 2018 by the authors. CycloDOPA (leukodopachrome), a well known metabolite of tyrosine, is a precursor of melanine in mammalian organisms and of the pigment betalain in plants. However, the isolation of cycloDOPA from natural sources has not been widely reported. In the present work, the stabilities of cycloDOPA and cycloDOPA methyl ester at various pH levels were studied. Both compounds were stable under acidic conditions. By contrast, both compounds were unstable when the pH was shifted from neutral to basic to form indole derivatives as major products. Based on the pH stability, cycloDOPA and its derivatives were subjected to the DPPH radical scavenging assay for the first time. - Tachrim, Zetryana Puteri, Oida, Kazuhiro, Ikemoto, Haruka, Ohashi, Fumina, Kurokawa, Natsumi, Hayashi, Kento, Shikanai, Mami, Sakihama, Yasuko, Hashidoko, Yasuyuki, Hashimoto, MakotoMOLECULES 22 (10) 1748 1420-3049 2017/10 [Refereed][Not invited]
Chiral N-protected alpha-amino aryl-ketones are one of the useful precursors used in the synthesis of various biologically active compounds and can be constructed via Friedel-Crafts acylation of N-protected alpha-amino acids. One of the drawbacks of this reaction is the utilization of toxic, corrosive and moisture-sensitive acylating reagents. In peptide construction via amide bond formation, N-hydroxysuccinimide ester (OSu), which has high storage stability, can react rapidly with amino components and produces fewer side reactions, including racemization. This study reports the first synthesis and utilization of N-trifluoroacetyl (TFA)-protected alpha-amino acid-OSu as a potential acyl donor for Friedel-Crafts acylation into various arenes. The TFA-protected isoleucine derivative and its diastereomer TFA-protected allo-isoleucine derivative were investigated to check the retention of alpha-proton chirality in the Friedel-Crafts reaction. Further utilization of OSu in other branched-chain and unbranched-chain amino acids results in an adequate yield of TFA-protected alpha-amino aryl-ketone without loss of optical purity. - Takuma Yoshida, Yasuyuki Hashidoko, Makoto HashimotoCHEMICAL SENSES 42 (8) E1 - E1 0379-864X 2017/10 [Refereed][Not invited]
- Makoto HashimotoPhotoaffinity Labeling for Structural Probing Within Protein 1 - 11 2017/09/25 [Refereed][Not invited]
The technique of photoaffinity labeling has become increasingly appreciated as a powerful methodology for post-genome field because it is one of the attractive methods to elucidate the interactions between bioactive ligand and biomolecule. The combinations with detection and isolation methods are essential to identify photolabeled components. There are several methods to introduce detection and isolation methods, which are so-called "tag," for photolabeled components from the photoaffinity label mixture. High detection limits of tag enable us to identify the photolabeled components. The introduction of detection and isolation tags in the ligand skeleton is one of the ways to archive identification of photolabeled components because the labeled components have been only introduced the tag. On the other hands, the specific biological interactions for target biomolecules are also utilized to identify photolabeled components. The chapter summarized that the several combinations of photoaffinity labeling and "tag" to study labeled components effectively. - Yuta Murai, Lei Wang, Makoto HashimotoPhotoaffinity Labeling for Structural Probing Within Protein 111 - 128 2017/09/25 [Refereed][Not invited]
As photophores in photoaffinity labeling, three major types, arylazide, benzophenone, and diazirine have been used and contributed to the understanding of molecular biology processes. In particular, diazrine is a significantly useful photophore because it has some advantages such as its relatively small size, stability, low rate of rearrangement, and generating a high reactive carbene with longer wavelength which reduces damage to the target molecules. Nevertheless, despite these many advantages in diazirine, there are reports in which arylazide and benzophenone are generally utilized for photoaffinity labeling compared with diazirine due to its synthetic difficulty onto ligands. To overcome this problem, recently many researchers have addressed to establish the efficient synthetic route of diazirinyl compounds. Particularly, a-aromatic amino acids possess not only biological activities themselves but also basic component of protein (bioactive peptide). In addition, a number of heterocyclic bioactive compounds have variety of attractive biological activities. Therefore, their diazirinyl compounds promise the molecular biology processes. In this chapter, firstly, it is demonstrated the simple and efficient preparation of diazirine on aromatics and aliphatic chains. Furthermore post-functional derivatization of them is also described to diversify bioactive compounds. - Lei Wang, Zetryana Puteri Tachrim, Natsumi Kurokawa, Fumina Ohashi, Yasuko Sakihama, Yasuyuki Hashidoko, Makoto HashimotoMOLECULES 22 (8) 1389 1420-3049 2017/08 [Refereed][Not invited]
Aliphatic diazirines have been widely used as prominent photophores for photoaffinity labeling owing to their relatively small size which can reduce the steric effect on the natural interaction between ligands and proteins. Based on our continuous efforts to develop efficient methods for the synthesis of aliphatic diazirines, we present here a comprehensive study about base-mediated one-pot synthesis of aliphatic diazirines. It was found that potassium hydroxide (KOH) can also promote the construction of aliphatic diazirine with good efficiency. Importantly, KOH is cheaper, highly available, and easily handled and stored compared with the previously used base, potassium tert-butoxide (t-BuOK). Gram-scale study showed that it owned great advantages in being used for the large-scale production of aliphatic diazirines. This protocol is highly neat and the desired products can be easily isolated and purified. As the first comprehensive study of the base-mediated one-pot synthesis of aliphatic diazirines, this work provided good insight into the preparation and utilization of diazirine-based photoaffinity labeling probes. - Zetryana Puteri Tachrim, Lei Wang, Yuta Murai, Takuma Yoshida, Natsumi Kurokawa, Fumina Ohashi, Yasuyuki Hashidoko, Makoto HashimotoCATALYSTS 7 (2) 40 2073-4344 2017/02 [Refereed][Not invited]
Trifluoromethanesulfonic acid (TfOH) is one of the superior catalysts for acylation. The catalytic activity of TfOH in C- and/or O-acylation has broadened the use of various substrates under mild and neat or forced conditions. In this review, the salient catalytic features of TfOH are summarized, and the unique controllability of its catalytic activity in the tendency of C-acylation and/or O-acylation is discussed. - Makoto Hashimoto, Takuma Yoshida, Zetryana Puteri Tachrim, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, Yuichi KanaokaHETEROCYCLES 95 (1) 462 - 473 0385-5414 2017/01 [Refereed][Not invited]
O-Benzylation of serine is one of the important protection methods for solid phase peptide synthesis. The utilities of the protection group may be indicated that chemical modifications for O-benzylserine will be utilized to make functional peptides on solid phase synthesis. Detailed studies for effective synthesis of photoreactive and fluorophore containing O-benzylserine derivatives without racemization were reported. - Akiko Ishida, Lei Wang, Zetryana Puteri Tachrim, Takeyuki Suzuki, Yasuko Sakihama, Yasuyuki Hashidoko, Makoto HashimotoCHEMISTRYSELECT 2 (1) 160 - 164 2365-6549 2017/01 [Refereed][Not invited]
Phenylthiourea (PTU) is well known as bioactive compound and one of the reversible inhibitors for tyrosinase. Tyrosinase plays very important roles for tyrosine metabolisms to maintain the skin homeostasis from sunlight with forming melanin. Synthesis of photoaffinity label reagents of PTU will be attractive thesis to elucidate functional analysis for tyrosinase. - Lei Wang, Akiko Ishida, Yasuyuki Hashidoko, Makoto HashimotoANGEWANDTE CHEMIE-INTERNATIONAL EDITION 56 (3) 870 - 873 1433-7851 2017/01 [Refereed][Not invited]
A novel strategy for the dehydrogenation of the NH-NH bond is disclosed using potassium tert-butoxide (tBuOK) in liquid ammonia (NH3) under air at room temperature. Its synthetic value is well demonstrated by the highly efficient synthesis of aromatic azo compounds (up to 100% yield, 3 min), heterocyclic azo compounds, and dehydrazination of phenylhydrazine. The broad application of this strategy and its benefit to chemical biology is proved by a novel, convenient, one-pot synthesis of aliphatic diazirines, which are important photoreactive agents for photoaffinity labeling. - Zetryana Puteri Tachrim, Lei Wang, Yasuyuki Hashidoko, Makoto HashimotoCHEMICAL SENSES 41 (9) E279 - E280 0379-864X 2016/11 [Refereed][Not invited]
- Lei Wang, Yasuyuki Hashidoko, Makoto HashimotoJOURNAL OF ORGANIC CHEMISTRY 81 (11) 4464 - 4474 0022-3263 2016/06 [Refereed][Not invited]
A cosolvent-promoted O-benzylation strategy with Ag2O was developed. The cosolvent consisting of CH2Cl2 and n-hexane can not only improve the reaction solubility for carbohydrates but also increase the benzylation efficiency. The formation of byproducts is greatly inhibited in the developed method. This method is simple, mild, and highly effective, and numerous 1'-benzylated sucrose derivatives were prepared including a photoreactive (trifluoromethyl)phenyldiazirine-based sucrose. The mechanisms of benzylation with primary and secondary benzyl bromides were also elaborated. Furthermore, the application scope with alcohols, glucose, and ribose derivatives was investigated. - Mengcen Wang, Seiji Tachibana, Yuta Murai, Li Li, Sharon Yu Ling Lau, Mengchao Cao, Guonian Zhu, Makoto Hashimoto, Yasuyuki HashidokoSCIENTIFIC REPORTS 6 2045-2322 2016/05 [Refereed][Not invited]
- Takuma Yoshida, Yasuyuki Hashidoko, Makoto HashimotoHETEROCYCLES 93 (1) 355 - 361 0385-5414 2016/04 [Refereed][Not invited]
Salicin is a substance that is well known for its bitter taste. Photoreactive benzophenone and phenylazide derivatives of salicin are for the functional analysis of interactions between the bitter taste receptor and salicin. First synthesis of these derivatives was prepared from acetobromo-alpha-D-glucose via glucosidation with salicylaldehyde derivatives followed by reduction of aldehyde to form salicin skeleton. - Yuta Murai, Takuma Yoshida, Lei Wang, Katsuyoshi Masuda, Yasuyuki Hashidoko, Kenji Monde, Yasumaru Hatanaka, Makoto HashimotoSYNLETT 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. - Mengcen Wang, Seiji Tachibana, Yuta Murai, Li Li, Sharon Yu Ling Lau, Mengchao Cao, Guonian Zhu, Makoto Hashimoto, Yasuyuki HashidokoSCIENTIFIC REPORTS 6 2045-2322 2016/03 [Refereed][Not invited]
Burkholderia heleia PAK1-2 is a potent biocontrol agent isolated from rice rhizosphere, as it prevents bacterial rice seedling blight disease caused by Burkholderia plantarii. Here, we isolated a non-antibacterial metabolite from the culture fluid of B. heleia PAK1-2 that was able to suppress B. plantarii virulence and subsequently identified as indole-3-acetic acid (IAA). IAA suppressed the production of tropolone in B. plantarii in a dose-dependent manner without any antibacterial and quorum quenching activity, suggesting that IAA inhibited steps of tropolone biosynthesis. Consistent with this, supplementing cultures of B. plantarii with either L-[ring-H-2(5)] phenylalanine or [ring-H-2(2-5)]phenylacetic acid revealed that phenylacetic acid (PAA), which is the dominant metabolite during the early growth stage, is a direct precursor of tropolone. Exposure of B. plantarii to IAA suppressed production of both PAA and tropolone. These data particularly showed that IAA produced by B. heleia PAK1-2 disrupts tropolone production during bioconversion of PAA to tropolone via the ring-rearrangement on the phenyl group of the precursor to attenuate the virulence of B. plantarii. B. heleia PAK1-2 is thus likely a microbial community coordinating bacterium in rhizosphere ecosystems, which never eliminates phytopathogens but only represses production of phytotoxins or bacteriocidal substances. - Zetryana Puteri Tachrim, Lei Wang, Takuma Yoshida, Miho Muto, Tadashi Nakamura, Katsuyoshi Masuda, Yasuyuki Hashidoko, Makoto HashimotoCHEMISTRYSELECT 1 (1) 58 - 63 2365-6549 2016/01 [Refereed][Not invited]
Regioselective halogenations of sucrose primary alcohols can simplify the synthesis of carbohydrate-based products. The Appel reaction, using carbon tetrahalide (CBr4 or CCl4) and triphenylphosphine, offers efficient conversion of primary hydroxyl groups to halide. Previous halogenation of sucrose with limited amounts of Appel reagent gave obscure result-regarding the halogenation selectivity of sucrose primary alcohols at 6-and 6'-position. Within careful purification of its per-O-acetylated form, re-subjection of sucrose into Appel reaction resulted in two mono-and one dihalogenated products only at 6-and/or 6'-position. Extensive NMR analyses support the revision of previous literature's assignments. Comprehensive analysis of each monohalogenated sucrose at the primary position, including the first reported 1'-monohalogenated sucrose derivatives synthesis via regioselective enzymic deacetylation, provided halogenation of sucrose primary alcohols by the Appel reaction followed the order of 6> 6'>> 1'. - Yoshida Takuma, Hashidoko Yasuyuki, Hashimoto MakotoThe Japanese Journal of Taste and Smell Research 日本味と匂学会 22 (3) 249 - 252 1340-4806 2015/12 [Not refereed][Not invited]
- Makoto Hashimoto, Takumi Misaka, Masaji Ishiguro, Katsuyoshi MasudaCHEMICAL SENSES 40 (8) 587 - 588 0379-864X 2015/10 [Refereed][Not invited]
- Lei Wang, Takuma Yoshida, Yasuyuki Muto, Yuta Murai, Zetryana Puteri Tachrim, Akiko Ishida, Shiori Nakagawa, Yasuko Sakihama, Yasuyuki Hashidoko, Katsuyoshi Masuda, Yasumaru Hatanaka, Makoto HashimotoEUROPEAN JOURNAL OF ORGANIC CHEMISTRY (14) 3129 - 3134 1434-193X 2015/05 [Refereed][Not invited]
Saccharin is one of the most common artificial sweeteners that has a bitter taste at high concentrations. Currently, there are no detailed functional analyses of these gustatory receptors. Therefore, we designed and synthesized photoreactive saccharin derivatives that contain a (trifluoromethyl) diazirinyl moiety at the 5- or 6-position for use as functional analysis tools for photoaffinity labeling. - Lei Wang, Yuta Murai, Takuma Yoshida, Akiko Ishida, Katsuyoshi Masuda, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, Makoto HashimotoORGANIC LETTERS 17 (3) 616 - 619 1523-7060 2015/02 [Refereed][Not invited]
Alternative one-pot synthesis of 3-(trifluoromethyl)-3-phenyldiazirine derivatives from corresponding tosyloximes is developed. The deprotonation of intermediate diaziridine by NH2- is a new approach for construction of diazirine. Moreover, a novel synthesis of optically pure (trifluoromethyl)diazirinylphenylalanine derivatives was attempted involving these methods. - Takuma Yoshida, Lei Wang, Shiori Nakagawa, Zetryana Puteri Tachrim, Yasuko Sakihama, Yasuyuki Hashidoko, Makoto HashimotoLETTERS IN ORGANIC CHEMISTRY 12 (8) 544 - 548 1570-1786 2015 [Refereed][Not invited]
Synthesis of cross-linkable diketopiperadine derivatives is described. Cross-linkable a-amino acid methyl esters were subjected to peptide synthesis with Boc-protected glycine or L-tyrosine. No protection of cross-linkable functional groups (catechol and phenylazide) is necessary for the construction of diketopiperazine skeleton. - Munenori Sakurai, Takuma Yoshida, Lei Wang, Yuta Murai, Katsuyoshi Masuda, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, Makoto HashimotoHETEROCYCLES 90 (1) 698 - 705 0385-5414 2015/01 [Refereed][Not invited]
Salicin (salicyl alcohol glucoside) is a substance well known for its bitter taste. A photoreactive diazirinyl derivative of salicin will be utilized for the functional analysis of interactions between the bitter taste receptor and salicin. Glucosides of salicyl derivatives are more difficult than phenol derivatives that are unsubstituted at the ortho-position. A diazirinyl salicin derivative was synthesized at moderate yields by glucosidation of 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide and 2-hydroxy-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzaldehyde in the presence of a phase-transfer catalyst, nBuEt(3)NBr, followed by reduction and deprotection. - Lei Wang, Yuta Murai, Takuma Yoshida, Masashi Okamoto, Katsuyoshi Masuda, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, Makoto HashimotoBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 78 (7) 1129 - 1134 0916-8451 2014/07 [Refereed][Not invited]
In this paper we report here a hydrogen/deuterium exchange (H/D exchange) of cross-linkable alpha-amino acid derivatives with deuterated trifluoromethanesulfonic acid (TfOD). H/D exchange with TfOD was easily applied to o-catechol containing phenylalanine (DOPA) within an hour. A partial H/D exchange was observed for trifluoromethyldiazirinyl (TFMD) phenylalanine derivatives. N-Acetyl-protected natural aromatic alpha-amino acids (Tyr and Trp) were more effective in H/D exchange than unprotected ones. The N-acetylated TFMD phenylalanine derivative afforded slightly higher H/D exchange than unprotected derivatives. An effective post-deuteration method for cross-linkable alpha-amino acid derivatives will be useful for the analysis of biological functions of bioactive peptides and proteins by mass spectrometry. - Lei Wang, Yuta Murai, Takuma Yoshida, Masashi Okamoto, Zetryana Puteri Tachrim, Yasuyuki Hashidoko, Makoto HashimotoMOLECULES 19 (5) 6349 - 6367 1420-3049 2014/05 [Refereed][Not invited]
Aryl-keto-containing alpha-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl alpha-amino acids, nonproteinogenic alpha-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing alpha-amino acids by Friedel-Crafts acylation using acidic alpha-amino acids as acyl-donors and Lewis acids or Bronsted acids as catalysts. - Makoto Hashimoto, Yuta MuraiJOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 72 (4) 360 - 369 0037-9980 2014/04 [Refereed][Invited]
Photoaffinity labeling is one of the favorite methods for chemical biology. The first step in this method is the construction of photophores and their modification to the associated high affinity target ligand. alpha-Amino acids have biological activities themselves and are fundamental component of peptides and protein. The photoreactive aromatic alpha-amino acids are useful for investigation of biological phenomenon. Although synthesis of photoreactive phenylalanine analogues has already been reported, there have been few reports of the synthesis of photoreactive tryptophan and side-chain elongated phenylalanine. We report here the effective photoreactive tryptophan and side-chain elongated phenylalanine derivatives. Furthermore, we report the mild and controllable hydrogen-deuterium exchange for aromatic hydrogen with trifluoromethanesulfonic acid-d during the course of the synthesis of side-chain elongated phenylalanine. These hydrogen-deuterium exchange properties for these aromatic alpha-amino acids are identical to those of the peptides. With this method the exchange proceeds significantly faster than previously described methods. Detail analysis of the exchange revealed that the method was controllable by temperature-, time-, and dose- dependent manner. - Lei Wang, Takuma Yoshida, Masashi Okamoto, Yasuko Sakihama, Yasuyuki Hashidoko, Makoto HashimotoMolBank 2014 (1) M816 1422-8599 2014/02/24 [Refereed][Not invited]
The title compound, which has two photoreactive groups in a molecule, was synthesized by the coupling reaction of 3-(4-(bromomethyl)phenyl)-3-(trifluoromethyl)- 3H-diazirine in the presence of silver oxide in DMSO. © 2014 by the authors licensee MDPI, Basel, Switzerland. - Sakurai, Munenori, Masuda, Katsuyoshi, Wang, Lei, Murai, Yuta, Sakihama, Yasuko, Hashidoko, Yasuyuki, Hatanaka, Yasumaru, Hashimoto, MakotoHETEROCYCLES 88 (1) 629 - 637 0385-5414 2014/01 [Refereed][Not invited]
Photoreactive phenylalanine derivatives are well known as functional analysis reagents for target biomolecules. The photophores are commonly introduced at 4-position on benzene. Aspartame, which consists of dipeptide L-Asp-L-Phe-OMe, is one of the most utilized artificial sweeteners, and substitution effects on its benzene ring have been reported. Substitution at the 4-position, however, does not maintain its sweetness properties. Trifluoromethyldiazirine, which is one of the most reliable photophores, was introduced to a different site on phenylalanine and the new photoreactive phenylalanine was converted to aspartame derivatives. The new aspartame derivative had slightly higher sweetness potency than sucrose standard solution. - Mengcen Wang, Makoto Hashimoto, Yasuyuki HashidokoPLOS ONE 8 (11) 1932-6203 2013/11 [Refereed][Not invited]
Background: The tropolone-tolerant Trichoderma virens PS1-7 is a biocontrol agent against Burkholderia plantarii, causative of rice seedling blight. When exposed to catechol, this fungus dose-dependently produced carot-4-en-9,10-diol,a sesquiterpene-type autoregulatory signal molecule that promotes self-conidiation of T. virens PS1-7 mycelia. It was, however, uncertain why T. virens PS1-7 attenuates the symptom development of the rice seedlings infested with B. plantarii. Methodology/Principal Findings: To reveal the antagonism by T. virens PS1-7 against B. plantarii leading to repression of tropolone production in a coculture system, bioassay-guided screening for active compounds from a 3-d culture of T. virens PS1-7 was conducted. As a result, carot-4-en-9,10-diol was identified and found to repress tropolone production of B. plantarii from 10 to 200 mu M in a dose-dependent manner as well as attenuate virulence of B. plantarii on rice seedlings. Quantitative RT-PCR analysis revealed that transcriptional suppression of N-acyl-L-homoserine lactone synthase plaI in B. plantarii was the main mode of action by which carot-4-en-9,10-diol mediated the quorum quenching responsible for repression of tropolone production. In addition, the unique response of B. plantarii to carot-4-en-9,10-diol in the biofilm formed in the static culture system was also found. Although the initial stage of B. plantarii biofilm formation was induced by both tropolone and carot-4-en-9,10-diol, it was induced in different states. Moreover, the B. plantarii biofilm that was induced by carot-4-en-9,10-diol at the late stage showed defects not only in matrix structure but also cell viability. Conclusions/Significance: Our findings demonstrate that carot-4-en-9,10-diol released by T. virens PS1-7 acts as an interkingdom cell-to-cell signaling molecule against B. plantarii to repress tropolone production and induces pseudo-biofilm to the cells. This observation also led to another discovery that tropolone is an autoregulatory cell-to-cell signaling molecule of B. plantarii that induces a functional biofilm other than a simple B. plantarii virulence factor. - Yuta Murai, Lei Wang, Yasuyuki Muto, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, Makoto HashimotoHETEROCYCLES 87 (10) 2119 - 2126 0385-5414 2013/10 [Refereed][Not invited]
Simple and stereocontrolled preparation of benzoylated phenylalanine derivatives from optically pure phenylalanine using Friedel-Crafts reaction in trifluoromethanesulfonic acid (TfOH) is reported; these derivatives are useful for photoaffinity labeling. Protected or unprotected phenylalanine derivatives were converted to benzoyl derivatives in TfOH at room temperature in a short time without loss of optical purity. The reaction condition was applied to synthesize novel photoreactive phenylalanine derivative, which has two photophores (benzophenone and diazirine). The detail analysis of photo-irradiation for two different photophores contained phenylalanine derivative was also investigated. - Lei Wang, Wataru Hisano, Yuta Murai, Munenori Sakurai, Yasuyuki Muto, Haruka Ikemoto, Masashi Okamoto, Takashi Murotani, Reika Isoda, Dongyeop Kim, Yasuko Sakihama, Irnayuli R. Sitepu, Yasuyuki Hashidoko, Yasumaru Hatanaka, Makoto HashimotoMOLECULES 18 (7) 8393 - 8401 1420-3049 2013/07 [Refereed][Not invited]
Photoaffinity labeling is a reliable analytical method for biological functional analysis. Three major photophores-aryl azide, benzophenone and trifluoromethyldiazirine-are utilized in analysis. Photophore-bearing L-phenylalanine derivatives, which are used for biological functional analysis, were inoculated into a Klebsiella sp. isolated from the rhizosphere of a wild dipterocarp sapling in Central Kalimantan, Indonesia, under nitrogen-limiting conditions. The proportions of metabolites were quite distinct for each photophore. These results indicated that photophores affected substrate recognition in rhizobacterial metabolic pathways, and differential photoaffinity labeling could be achieved using different photophore-containing L-phenylalanine derivatives. - Yuta Murai, Katsuyoshi Masuda, Yui Ogasawara, Lei Wang, Yasuyuki Hashidoko, Yasumaru Hatanaka, So Iwata, Takuya Kobayashi, Makoto HashimotoEuropean Journal of Organic Chemistry 2013 (12) 2428 - 2433 1434-193X 2013/04 [Refereed][Not invited]
2-Phenylethylamine is well known as a substructure of many biologically active compounds, and the synthesis of its photoreactive derivatives to allow the analysis of biological functions is reported. This allowed us to synthesise ligands for adenosine receptors, which have many functional roles in biology and have been extensively studied for their many roles in maintaining homeostasis. Adenosine is one of the most common biochemical compounds, but photoaffinity labeling has not yet been used to study adenosine receptors. Synthetic methods for producing photoreactive adenosine derivatives that can be used with adenosine receptors were established for the photophores phenyl azide and benzophenone. The effect of the introduction of the photoreactive components was determined using an adenosine receptor assay. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. - Mengcen Wang, Makoto Hashimoto, Yasuyuki HashidokoAPPLIED AND ENVIRONMENTAL MICROBIOLOGY 79 (6) 1906 - 1914 0099-2240 2013/03 [Refereed][Not invited]
To screen biocontrol agents against Burkholderia plantarii, the causative agent of rice seedling blight, we employed catechol, an analog of the virulence factor tropolone, to obtain chemical stress-resistant microorganisms. The fungal isolate PS1-7, identified as a strain of Trichoderma virens, showed the highest resistance to catechol (20 mM) and exhibited efficacy as a biocontrol agent for rice seedling blight. During investigation of metabolic traits of T. virens PS1-7 exposed to catechol, we found a secondary metabolite that was released extracellularly and uniquely accumulated in the culture. The compound induced by chemical stress due to catechol was subsequently isolated and identified as a sesquiterpene diol, carot-4-en-9,10-diol, based on spectroscopic analyses. T. virens PS1-7 produced carot-4-en-9,10-diol as a metabolic response to tropolone at concentrations from 0.05 to 0.2 mM, and the response was enhanced in a dose-dependent manner, similar to its response to catechol at concentrations from 0.1 to 1 mM. Some iron chelators, such as pyrogallol, gallic acid, salicylic acid, and citric acid, at 0.5mM also showed activation of T. virens PS1-7 production of carot-4-en-9,10-diol. This sesquiterpene diol, formed in response to chemical stress, promoted conidiation of T. virens PS1-7, suggesting that it is involved in an autoregulatory signaling system. In a bioassay of the metabolic and morphological responses of T. virens PS1-7, conidiation in hyphae grown on potato dextrose agar (PDA) plates was either promoted or induced by carot-4-en-9,10-diol. Carot-4-en-9,10-diol can thus be regarded as an autoregulatory signal in T. virens, and our findings demonstrate that intrinsic intracellular signaling regulates conidiation of T. virens. - Yuta Murai, Lei Wang, Katsuyoshi Masuda, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, Makoto HashimotoEuropean Journal of Organic Chemistry 2013 (23) 5111 - 5116 1434-193X 2013 [Refereed][Not invited]
Novel hydrogen/deuterium exchange for aromatic α-amino acids and their corresponding peptides were performed through the use of deuterated trifluoromethanesulfonic acid (TfOD). Detailed analysis of the exchange revealed that equal hydrogen/deuterium exchange was observed for phenylalanine, and specific exchange at the ortho-positions of phenol for tyrosine was also detected. The stereochemistry of the aromatic α-amino acids was retained under the exchange conditions. The hydrogen/deuterium exchange properties for these aromatic α-amino acids are identical for peptides that contain several aromatic α-amino acids. The exchange proceeded significantly faster than previous methods. Detailed analysis of the exchange revealed that the method could be controlled by temperature, time, and the amount of reagent. Deuterated trifluoromethanesulfonic acid promotes rapid and controllable hydrogen/deuterium exchange on aromatic rings of α-amino acids and peptides at room temperature and below. The deuterium incorporation depends on the amount of reagent, the temperature, and the time-scale of the reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. - Yui Ogasawara, Yuta Murai, Yasuko Sakihama, Yasuyuki Hashidoko, Makoto HashimotoHETEROCYCLES 86 (1) 735 - 743 0385-5414 2012/12 [Refereed][Not invited]
The click reaction is one of the latest techniques for the chemical modification of bioactive compounds. Chemical modifications of alpha-amino acid side chains are gaining significance as useful and important tools for biochemical research. Biotinylation at side chain of propargylglycine using click reaction was examined. The detail quantitative analysis of Cu(I) concentration are performed to proceed the click reaction effectively. - Yasuyuki Muto, Yuta Murai, Yasuko Sakihama, Yasuyuki Hashidoko, Makoto HashimotoBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 76 (11) 2162 - 2164 0916-8451 2012/11 [Refereed][Not invited]
Biotin is one of the most useful tags in (bio)analytical science due to its specific interaction with avidin, but is not easy to convert because of its low solubility in most solvents. Friedel-Crafts acylation of biotin acid chloride in triflic acid was examined, and the synthesized derivatives had stronger affinity to avidin than biotin in a binding assay using 2-(4'-hydroxyphenylazo)benzoic acid. - Yuta Murai, Katsuyoshi Masuda, Yasuko Sakihama, Yasuyuki Hashidoko, Yasumaru Hatanaka, Makoto HashimotoJOURNAL OF ORGANIC CHEMISTRY 77 (19) 8581 - 8587 0022-3263 2012/10 [Refereed][Not invited]
5- and 6-trifluoromethyldiazirinyl indoles were synthesized from corresponding bromoindole derivatives for the first time. They acted as mother skeletons for the comprehensive synthesis of various bioactive indole metabolites. These can be used in biological functional analysis as diazirine-based photoaffinity labels. - Yuka Tsunekawa, Katsuyoshi Masuda, Miho Muto, Yasuyuki Muto, Yuta Murai, Yasuyuki Hashidoko, Yoshitake Orikasa, Yuji Oda, Yasumaru Hatanaka, Makoto HashimotoHETEROCYCLES 84 (1) 283 - 290 0385-5414 2012/01 [Refereed][Not invited]
As the 1'-hydroxyl group of sucrose is well known to be less reactive than other primary alcohols, there are no reports on the substitution of a phenoxy group at this position. Chemo-enzymatic synthesis of photoreactive 1'-phenoxy-substituted sucrose was examined to elucidate the functional analysis of sweet receptors. - Yui Ogasawara, Yuta Murai, Yasuko Sakihama, Yasuyuki Hashidoko, Makoto HashimotoInternational Journal of Organic Chemistry Scientific Research Publishing 02 (03) 302 - 304 2161-4687 2012The click reaction is one of the latest techniques for the functional analysis of bioactive compounds and the analysis makes novel concepts and strategies for medicinal chemistry. N-methylated glycine derivatives have inhibitory activity for the click reaction in direct Cu(I) system because of decrease of Cu(I) concentration. The Cu(I) concentration recovered effectively by sodium ascorbate. Quantitative determination of click reaction at various ligand concentrations revealed that the decrease in reaction yields was observed in a substrate concentration-dependent manner.
- Yasuko Sakihama, Makiko Maeda, Makoto Hashimoto, Satoshi Tahara, Yasuyuki HashidokoFREE RADICAL RESEARCH 46 (1) 93 - 99 1071-5762 2012/01 [Refereed][Not invited]
Two major betalains, red-purple betacyanins and yellow betaxanthins, were isolated from red beetroots (Beta vulgaris L.), and their peroxynitrite (ONOO(-)) scavenging capacity was investigated. Apparent colours of the betalains were bleached by the addition of ONOO(-), and the absorbance decreases were suppressed in the presence of glutathione, a ONOO(-) scavenger. After bleaching, a new absorption maximum was observed at 350 nm in the spectrum of the resulting reaction mixture. New peaks were detected from HPLC analysis of the reaction products of betanin, a representative constituent of red beetroot betacyanins, treated with ONOO(-) monitoring at 350 nm, and the intensity of the major peak was positively correlated with ONOO(-) concentration. Betanin inhibited the ONOO(-) (0.5 mM)-dependent nitration of tyrosine (0.1 mM). Additionally, the IC(50) value of betanin (19.2 mu M) was lower than that of ascorbate (79.6 mu M). The presence of betanin (0.05-1.0 mM) also inhibited ONOO(-) (0.5 mM)-dependent DNA strand cleavage in a concentration -dependent manner. These results suggest that betalains can protect cells from nitrosative stress in addition to protecting them from oxidative stresses. - Yuta Murai, Yasuyuki Hashidoko, Makoto HashimotoBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 75 (2) 352 - 354 0916-8451 2011/02 [Refereed][Not invited]
We report here a novel synthesis of optically active bishomotyrosine. The bishomotyrosine skeleton was constructed by using a Friedel-Crafts reaction between phenol and optically active N-Tfa-Glu(Cl)-OMe in triflic acid under the mild condition. Reduction and subsequent deprotection then afforded bishomotyrosine derivatives without any loss of optical purity. - Ryo Murashige, Yuka Hayashi, Syo Ohmori, Ayuko Torii, Yoko Aizu, Yasuyuki Muto, Yuta Murai, Yuji Oda, Makoto HashimotoTETRAHEDRON 67 (3) 641 - 649 0040-4020 2011/01 [Refereed][Not invited]
Reactions involving phenol derivatives and acyl chlorides have to be controlled for competitive O-acylations and C-acylations (Friedel Crafts acylations and Fries rearrangements) in acidic condition. The extent for these reactions in trifluoromethanesulfonic acid (TfOH), which is used as catalyst and solvent, is examined. Although diluted TfOH was needed for effective O-acylation, concentrated TfOH was required for effective C-acylations in mild condition. These results have been applied to the novel synthesis of homotyrosine derivatives. Both Fries rearrangement of N-TFA-Asp(OBn)-OMe and Friedel-Crafts acylation of phenol with N-TFA Asp(Cl)-OMe in TfOH afforded the homotyrosine skeleton, followed by reduction and deprotection afforded homotyrosines maintaining stereochemistry of Asp as an optically pure form. (C) 2010 Elsevier Ltd. All rights reserved. - Yuta Murai, Miho Takahashi, Yasuyuki Muto, Yasumaru Hatanaka, Makoto HashimotoHETEROCYCLES 82 (1) 909 - 915 0385-5414 2010/12 [Not refereed][Not invited]
Post-functional deuterium incorporation into diazirinyl acetophenone derivatives is reported. Treatment of the compounds with sodium hydroxide in CH3OD at rt for 10 min achieved deuterium incorporation at alpha-position of the carbonyl group without decomposition of diazirinyl ring. Further deuterium can introduce by reduction of benzyl carbonyl with triethylsilane-d-TFA. Straightforward deuterium introduction into diazirinyl derivatives may contribute to the functional analysis of low molecular compounds with diazirine-based photoaffinity labeling. - Makoto Hashimoto, Keitaro Furukawa, Takenori Tomohiro, Yasumaru HatanakaCHEMICAL & PHARMACEUTICAL BULLETIN 58 (3) 405 - 407 0009-2363 2010/03 [Refereed][Not invited]
Synthesis of diazirinyl organo-platinum complexes, which specifically interact with purine base, characterization of photoreactivity and interaction between guanosine 5'-monophosphate (GMP) were examined. The results indicated that the diazirinyl organo-platinum complex was useful for manipulations of photoaffinity labeled components. - Yasunori Kushi, Hisashi Kamimiya, Hiroko Hiratsuka, Hirofumi Nozaki, Hiroshi Fukui, Mayumi Yanagida, Makoto Hashimoto, Kimihide Nakamura, Shinobu Watarai, Takeshi Kasama, Hitomi Kajiwara, Takeshi YamamotoGLYCOBIOLOGY 20 (2) 187 - 198 0959-6658 2010/02 [Refereed][Not invited]
Bacterial sialyltransferases (STs) from marine sources were characterized using glycosphingolipids (GSLs). Bacterial STs were found to be beta-galacotoside STs. There were two types of STs: (1) ST obtained from strains such as ishi-224, 05JTC1 (#1), ishi-467, 05JTD2 (#2), and faj-16, 05JTE1 (#3), which form alpha 2-3 sialic acid (Sia) linkages, named alpha 2-3ST, (2) ST obtained from strains such as ISH-224, N1C0 (#4), pda-rec, 05JTB2 (#5), and pda-0160, 05JTA2 (#6), which form alpha 2-6 Sia linkages, named alpha 2-6ST. All STs showed affinity to neolacto- and lacto-series GSLs, particularly in neolactotetraosyl ceramide (nLc(4)Cer). No large differences were observed in the pH and temperature profiles of enzyme activities. Kinetic parameters obtained by Lineweaver-Burk plot analysis showed that #3 and #4 STs had practical synthetic activity and thus it became easily possible to achieve large-scale ganglioside synthesis (100-300 mu M) using these recombinant enzymes. Gangliosides synthesized from nLc(4)Cer by alpha 2-3 and alpha 2-6STs were structurally characterized by several analytical and immunological methods, and they were identified as IV(3)alpha NeuAc-nLc(4)Cer(S2-3PG) and IV(6)alpha NeuAc-nLc(4)Cer (S2-6PG), respectively. Further characterization of these STs using lactotetraosylceramide (Lc(4)Cer), neolactohexaosylceramide (i antigen), and IV(6)kladoLc(8)Cer (I antigen) showed the synthesis of corresponding gangliosides as well. Synthesized gangliosides showed binding activity to the influenza A virus [A/panama/2007/99 (H3N2)] at a similar level to purified S2-3PG and S2-6PG from mammalian sources. The above evidence suggests that these STs have unique features, including substrate specificities restricted to lacto- and neolactoseries GSLs, as well as catalytic potentials for ganglioside synthesis. This demonstrates that efficient in vitro ganglioside synthesis could be a valuable tool for selectively synthesizing Sias modifications, thereby permitting the exploration of unknown functions. - Katsuyoshi Masuda, Ayako Koizumi, Takumi Misaka, Yasumaru Hatanaka, Keiko Abe, Takaharu Tanaka, Masaji Ishiguro, Makoto HashimotoBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 20 (3) 1081 - 1083 0960-894X 2010/02 [Refereed][Not invited]
Some D-Amino acids such as D-tryptophan and D-phenylalanine are well known as naturally-occurring sweeteners. Photoreactive D-phenylalanine derivatives containing trifluoromethyldiazirinyl moiety at 3- or 4-position of phenylalanine, were designed as sweeteners for functional analysis with photoaffinity labeling. The trifluoromethyldiazirinyl D-phenylalanine derivatives were prepared effectively with chemo-enzymatic methods using L-amino acid oxidase and were found to have potent activity toward the human sweet taste receptor. (C) 2009 Elsevier Ltd. All rights reserved. - Ryo Murashige, Yuta Murai, Yasumaru Hatanaka, Makoto HashimotoBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 73 (6) 1377 - 1380 0916-8451 2009/06 [Refereed][Not invited]
The Friedel-Crafts reaction with 3-(3-methoxy-phenyl)-3-(trifluoromethyl)-3H-diazirine and optically active N-TFA-Asp(Cl)-OMe in triflic acid afforded homophenylalanine derivatives without any loss of the optical purity. - Yuta Murai, Yasumaru Hatanaka, Yulichi Kanaoka, Makoto HashimotoHETEROCYCLES 79 359 - 364 0385-5414 2009/04 [Refereed][Not invited]
Effective incorporation of phenyldiazirine moiety on the acyl residue of (L)- and (D)- glutamic acid by Friedel-Crafts reactions with triflic acid developed simple preparation of bishomophenylalanine (bhPhe) for aromatics, which added a versatile and a reliable access to photoreactive peptide probes. - Mayumi Sato, Kazuto Seki, Kazuhito Kita, Yoshinari Moriguchi, Makoto Hashimoto, Keita Yunoki, Masao OhnishiJOURNAL OF WOOD SCIENCE 55 (1) 32 - 40 1435-0211 2009/02 [Refereed][Not invited]
The diterpene compositions in the bark of branches were investigated for two families of the F-1 hybrid, Kurile larch (Larix gmelinii var. japonica Pilg.) x Japanese larch [Larix kaempferi (Lamb.) Carr.] (hereafter F-1) and their parents clones. 13-Epimanool, larixol, larixyl acetate, 13-epitorulosyl acetate (not detected in L. gmelinii var. japonica), isopimaric acid, abietic acid, dehydroabietic acid, and neoabietic acid were detected. Larixol and abietic acid represented more than 50% of the diterpene content in L. gmelinii var. japonica and L. kaempferi, respectively. Larixol and abietic acid were the predominant diterpene components in the F-1, and the proportions of these diterpenes were between those of the parental species. Therefore, the diterpene compositions in the F-1 were hereditarily infl uenced by their parents. The ratios of labdane, pimarane, and abietane diterpenes suggested that the main diterpene biosynthesis pathway in L. gmelinii var. japonica was from copalyl diphosphate (CDP) to labdane-type diterpenes, and that in L. kaempferi was from CDP to abietane-type diterpenes via pimarane type. Furthermore, linear discriminant analysis suggested that the diterpene contents are effective indices for the discrimination of the hybrid seedlings. - Makoto Hashimoto, Miho TakahashiHETEROCYCLES 77 (1) 227 - 231 0385-5414 2009/01 [Refereed][Not invited]
Triflic acid is well known not only as a Friedel-Crafts promoter, but also as a deglycosidation reagent. In this study, we promote effective Friedel-Crafts acylations for O- or C-arylglucosides without deglycosidation and check their inhibitory activities for P-glucosidase. - Hiroko Hiratsuka, Hirofumi Nozaki, Hiroshi Fukui, Mayumi Yanagida, Makoto Hashimoto, Hisashi Kamimiya, Shinobu Watarai, Takeshi Kasama, Hitomi Kajiwara, Takeshi Yamamoto, Yasunori Kushi, Kimihide NakamuraGLYCOBIOLOGY 18 (11) 996 - 996 0959-6658 2008/11 [Refereed][Not invited]
- Ryo Murashige, Yuka Hayashi, Makoto HashimotoTETRAHEDRON LETTERS 49 (46) 6566 - 6568 0040-4039 2008/11 [Refereed][Not invited]
An efficient Friedel-Crafts reaction of TFA-Asp(Cl)-OMe and stoichiometric amounts of benzene was established by using neat trifluoromethanesulfonic acid (TfOH) as solvent and catalyst under a mild condition. This methodology has been applied to many aromatic compounds and enabled synthesis of several homophenylalanine derivatives. (C) 2008 Elsevier Ltd. All rights reserved. - Makoto Hashimoto, Yasumaru HatanakaEUROPEAN JOURNAL OF ORGANIC CHEMISTRY (15) 2513 - 2523 1434-193X 2008/05 [Refereed][Invited]
As a result of recent developments in molecular biology, the investigation of biofunctional machinery at ligand-accepting interfaces has become one of the challenging and important subjects in the post-genome field. The technique of photoaffinity labeling has become increasingly appreciated as a powerful methodology for this purpose. This microreview focuses on the synthesis of 3-phenyl-3-(trifluoromethyl)diazirine, one of the most promising photophores, and its application to biomolecules. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008). - Makoto Hashimoto, Yasumaru HatanakaBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 18 (2) 650 - 652 0960-894X 2008/01 [Refereed][Not invited]
A novel photoreactive ceramide analogue, which contains (3-trifluoromethyl)phenyldiazirinyl lipid and biotinylated sphingosine, was synthesized. The probe was recognized as an antigen by anti-ceramide antibody and as a substrate for sphingolipid ceramide N-deacylase. These results indicate that the probe may be useful as a photoaffinity-biotinylating agent in sphingolipid studies. (c) 2007 Elsevier Ltd. All rights reserved. - Makoto Hashimoto, Yuh-Hi Kato, Yasumaru HatanakaCHEMICAL & PHARMACEUTICAL BULLETIN 55 (10) 1540 - 1543 0009-2363 2007/10 [Refereed][Not invited]
Selective hydrogenation of carbon-carbon double bond in the presence of nitrogen-nitrogen double bond in (3-trifluoromethyl) phenyidiazirine achieved with Wilkinson's catalyst. - Sun-Ju Kim, Chiami Kawaharada, Shigeki Jin, Makoto Hashimoto, Gensho Ishii, Hiroaki YamauchiBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 71 (1) 114 - 121 0916-8451 2007/01 [Refereed][Not invited]
The structurally unique glucosinolate (GSL), 4-(cystein-S-yl)butyl GSL, was identified in the leaves of hydroponically-grown rocket salad (Eruca sativa Mill.). Its electrospray ionization mass spectrometry (ESI-MS)/MS spectrum indicated that this unusual GSL had a molecular weight of 414 as a desulfo (DS)-GSL, and a molecular formula of C14H25N2O8S2 based on its negative ion matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) spectrum. For further confirmation, the 4-(cystein-S-yl)butyl DS-GSL was prepared with authentic L-Ser and purified dimeric 4-mercaptobutyl DS-GSL, and its chemical structure then confirmed by ESI-MS/MS data. It is named "glucorucolamine" as a trivial name from its ammonia sensitivity. This unique GSL was found to the greatest extent when rocket salad was grown in a 100% NH4+-N nutrient solution. Despite it clearly seems to reduce the detoxification of excess NH4+ in the leaves of rocket salad, present knowledge about the unique GSL is still far from being sufficient. - Leily Tjandrawaskitasari, Rie Hata, Hanarni Chiba, Makoto Hashinioto, Kosaku Takahashi, Kensuke NabetaNATURAL PRODUCT COMMUNICATIONS 2 (6) 663 - 670 1934-578X 2007 [Refereed][Not invited]
Peroxidase secretion and activity in the oxidation of polyphenols bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl)propane) and lignin model compound (LMC, guaiacylglycerol-beta-gualacylether) were observed in a suspension cell culture of liverwort Heteroscyphus planus. When BPA was co-incubated in a suspension cell culture of liverwort for 5 days, it was depleted by approximately 63%. Oxidation of BPA was observed in culture filtrates of liverwort, and most of the oxidation products were insoluble higher molecular-weight compounds (30%). The oxidative degradation products of BPA and LMC were analyzed by GC-MS and were identified by comparing their retention time and MS spectra with those of the authentic compounds. BPA was degraded to 4-isopropenylphenol and p-hydroxyacetophenone. The formation of these products was examined using [H-1(14)]-BPA. The lignin model compound was degraded to guaiacol, vanillin, coniferyl alcohol and ferulic acid. Biphenyl dehydrodimer was detected in both the reaction mixtures of the suspension cell culture and the culture filtrates incubated with the LMC. The dimer was identified as 1, l'-(4,4'-dihydroxy-3,3'-dimethoxy-5,5'-biphenylene)- bis[8-(2 ''-methoxyphenoxy)-7,9propanediol] by 1D and 2D NMR analysis. The activity of secreted peroxidase in the suspension cell culture (0.045 U/mL) was slightly enhanced by addition of LMC (0.059 U/mL), p-cresol (0.064 U/mL), and 2,6-dimethoxyphenol (0.082 U/mL) 7 days after the beginning of incubation. - Makoto Hashimoto, Yasumaru HatanakaBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 16 (23) 5998 - 6000 0960-894X 2006/12 [Refereed][Not invited]
Novel diazirinyl photoaffinity ligand, which contains (3-trifluoromethyl) phenyldiazirine and penta(epsilon-Boc-Lys) as a photoreactive code, allows the introduction of a positive cascade to alter the pI value of labeled components, facilitating the isolation of photolabeled biocomponents with isoelectric focusing techniques. (c) 2006 Elsevier Ltd. All rights reserved. - Kyu-Ho Han, Mitsuo Sekikawa, Ken-ichiro Shimada, Makoto Hashimoto, Naoto Hashimoto, Takahiro Noda, Hisashi Tanaka, Michihiro FukushimaBRITISH JOURNAL OF NUTRITION 96 (6) 1125 - 1133 0007-1145 2006/12 [Refereed][Not invited]
Anthocyanins from various vegetables and fruits have antioxidant activities, however, the bioactivities of coloured potato anthocyanins are not well studied. We examined the antioxidant capacities of pigmented fractions from purple potato flakes in vitro, and the antioxidant potentials of purple potato flakes in vivo. 1,1-Diphenyl-2-picrylhydrazyl radical scavenging activity of the pigmented fraction from Hokkai no. 92 (H92) potato flakes was higher than that from Kitamurasaki (KM) potato flakes. Extracts equivalent to 600 mu g pigmented fractions from KM and H92 potato flakes inhibited linoleic acid oxidation in the order trolox > H92 >= KM > control. Rats were fed 25 % KM or H92 potato flake diets for 4 weeks. The major anthocyanin was identified as petanin. Control rats were fed a diet with cornstarch instead of potato flakes for 4 weeks. The serum antioxidant potential level in the H92 group was significantly higher than that in the control group. The degree of hepatic lipid peroxidation in the H92 group was significantly lower than that in the control group. Hepatic Cu/Zn-superoxide dismutase (SOD), Mn-SOD and glutathione peroxidase (GSH-Px) mRNA levels in the H92 group were significantly higher than those in the control group. Similar significant differences in Cu/Zn-SOD and Mn-SOD mRNA levels between the KM and control groups were found. The present results suggest that purple potato flakes have antioxidant functions with regard to radical scavenging activity and inhibition of linoleic acid oxidation, and that they improve the antioxidant potentials in rats by enhancing hepatic Mn-SOD, Cu/Zn-SOD and GSH-Px mRNA expression. - Hiroyuki Nakashima, Makoto Hashimoto, Yutaka Sadakane, Takenori Tomohiro, Yasumaru HatanakaJOURNAL OF THE AMERICAN CHEMICAL SOCIETY 128 (47) 15092 - 15093 0002-7863 2006/11 [Refereed][Not invited]
- Kyu-Ho Han, Naoto Hashimoto, Makoto Hashimoto, Takahiro Noda, Ken-ichiro Shimada, Chi-Ho Lee, Mitsuo Sekikawa, Michihiro FukushimaBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 70 (9) 2285 - 2288 0916-8451 2006/09 [Refereed][Not invited]
The protective effects of red potato extract (RPE) as to liver damage were determined in D-galactosamine (GaIN)-intoxicated rats. Increases in serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities, all of which were induced by GaIN injection, decreased in RPE administered rats, suggesting that RPE acts as a functional food showing anti-hepatotoxicity. - Hashimoto Makoto, Hatanaka YasumaruInternational Symposium on the Chemistry of Natural Products 天然有機化合物討論会 2006 "P - 444" 2006/07/23
- Kyu-Ho Han, Naoto Hashimoto, Ken-ichiro Shimada, Masuo Sekikawa, Takahiro Noda, Hiroaki Yamauchi, Makoto Hashimoto, Hideyuki Chiji, David L. Topping, Michihiro FukushimaBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 70 (6) 1432 - 1437 0916-8451 2006/06 [Refereed][Not invited]
We investigated the hepatoprotective effect of purple potato extract (PPE) agalNst D-galactosamine (galN)-induced liver injury in rats. PPE (400 mg) was administered once daily for 8 d, and then galN (250 mg/kg of body weight) was injected at 22 h before the rats were killed. Serum tumor necrosis factor alpha (TNF-alpha), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and asparate aminotranferase (AST) levels increased significantly after injection of galN, but PPE inhibited GalN-induced alterations in serum TNF-a, LDH, ALT, and AST levels. Hepatic lipid peroxide and glutathione levels in the control + galN group were higher and lower respectively than those in the control group, and those in the PPE + galN group did not differ from that in the control group. The lipid peroxide level in hepatic microsomes treated with 2,2'-azobis (2-amidinopropane) dihydrochloride in the PPE group was significantly lower than that in the control group. This suggests that PPE has hepatoprotective effects agalNst GalN-induced hepatotoxicity via inhibition lipid peroxidation and/or inflammation in rats. - M Hashimoto, Y Kato, Y HatanakaTETRAHEDRON LETTERS 47 (20) 3391 - 3394 0040-4039 2006/05 [Refereed][Not invited]
A simple and mild method was developed for the introduction of iodo-label on (3-trifluoromethyl) phenyidiazirine (TPD) aromatic ring in the presence of three membered diazirine ring. An iodination protocol, I-2-BTI in CH3CN, was found to be effective even though affinity ligands are pre-installed. (c) 2006 Elsevier Ltd. All rights reserved. - M Hashimoto, Y HatanakaANALYTICAL BIOCHEMISTRY 348 (1) 154 - 156 0003-2697 2006/01 [Refereed][Not invited]
- M Hashimoto, Y HatanakaHETEROCYCLES 66 531 - 534 0385-5414 2005/12 [Refereed][Not invited]
3-Trifluoromethylphenyldiazirinylated diol derivative was utilized to introduce an aldehyde by periodate oxidation, followed by the formation of a Schiff base with biotin hydrazide on a PVDF membrane for post-labeling of photocrosslinked proteins. The biotin hydrazide was able to post-label the 2.5 x 10(-13) mole of closslinked component for chemiluminescent visualization. - M Hashimoto, Y HatanakaCHEMICAL & PHARMACEUTICAL BULLETIN 53 (11) 1510 - 1512 0009-2363 2005/11 [Refereed][Not invited]
Post-biotinylation of the alkyl azide derivative of trifluoromethyl phenyldiazirine (TPD) was elucidated to apply a photoaffinity biotinylation technique. A photo-modified polyvinilidene difluoride (PVDF) membrane was used as a photolabeled component and we introduced biotin by Staudinger-Bertozzi ligation. The 15 pmol amount of biotinylated reagent was still effective for the visualization of cross-linked product on the matrix. The results show the potential utility of alkyl azide carrying TPD derivatives in the application of photoaffinity biotinylation, which could be useful for the ligands with tight structural requirements. - M Hashimoto, T Komano, K Nabeta, Y HatanakaCHEMICAL & PHARMACEUTICAL BULLETIN 53 (1) 140 - 142 0009-2363 2005/01 [Refereed][Not invited]
A convenient procedure for the synthesis of (E)- and (Z)-beta-bromostyrene containing trifluoromethyldiazirine is described, which involves the stereoselective reduction of the corresponding trifluoromethyldiazirinyl beta,beta-dibromostyrene without damaging the photophor. The synthetic route easily introduced deuterium, which can be utilized for the detection of a photolabeled component by MS spectrometry, after construction of a trifluoromethyldiazirinyl skeleton. - T Tomohiro, M Hashimoto, Y HatanakaCHEMICAL RECORD 5 (6) 385 - 395 1527-8999 2005 [Refereed][Not invited]
An efficient method of photoaffinity labeling has been developed based on rationally designed multifunctional photoprobes. Photoaffinity techniques have been used to elucidate the protein structure at the interface of biomolecules by the photochemical labeling of interacting sites. However, the identification of labeled sites within target proteins is often difficult. Novel biotinyl bioprobes bearing a diazirine photophore have contributed significantly to the rapid elucidation of ligand binding sites within proteins, thereby extending conventional phoroaffinity methods. This article discusses the synthesis and applications of various photoprobes bearing a biotin, including strategies using cleavable linkages between photophores. The combination of photoaffinity methods with chip technology is also described as a novel entry to rapid affinity-based screening of inhibitors. This review focuses on a rapid and reliable photoaffinity method utilizing diazirine-based multifunctional photoprobes with numerous potential applications in functional proteomics of biomolecular interactions. (c) 2005 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. - M Hashimoto, Y HatanakaCHEMICAL & PHARMACEUTICAL BULLETIN 52 (11) 1385 - 1386 0009-2363 2004/11 [Refereed][Not invited]
The synthesis of trifluoromethyl diazirine with a stable isotope tag is reported. We found that both Friedel-Crafts acylation and reduction of aryl carbonyl to methylene, using commercially available stable-isotope reagents, were utilized for the synthesis of diazirinyl fatty acid derivatives. The stable isotope labeled diazirine may be valuable for identifying binding sites by mass spectrometry. - M Hashimoto, S Okamoto, K Nabeta, Y HatanakaBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 14 (10) 2447 - 2450 0960-894X 2004/05 [Refereed][Not invited]
The efficient synthesis of an enzyme cleavable biotinylated diazirinyl photoaffinity ligand is described to allow the effective manipulation of the photolabeled biocomponents. The compound contains a glutamic acid gamma-methyl ester, which is a precursor of the substrate for V8 protease, between the diazirinyl photophor and biotin moiety. After alkaline hydrolysis of the ester, the compound can be proteolyzed at the Glu moiety by V8 protease. The photophore was introduced to L-Phe p-nitroanilide and the ligand was applied to photolabel of chymotrypsin to manipulate the application of the concept. (C) 2004 Elsevier Ltd. All rights reserved. - P Whitley, BJ Reaves, M Hashimoto, AM Riley, BVL Potter, GD HolmanJOURNAL OF BIOLOGICAL CHEMISTRY 278 (40) 38786 - 38795 0021-9258 2003/10 [Refereed][Not invited]
Phosphatidylinositol 3,5-bisphosphate is a membrane lipid found in all eukaryotes so far studied but down-stream effector proteins of this lipid have yet to be identified. Here we report the use of cDNA phage libraries in conjunction with synthetic biotinylated derivatives of phosphatidylinositol 3,5-bisphosphate in the identification of a mammalian phosphatidylinositol 3,5-bisphosphate-binding protein, mVps24p. This protein is orthologous to the Saccharomyces cerevisiae protein, Vps24p, a class-E vacuolar protein-sorting protein. Using in vitro liposome binding and competition assays, we demonstrate that mVps24p selectively binds to phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4-bisphosphate in preference to other phosphoinositides tested. When expressed in cultured mammalian cells, full-length mVps24p is cytosolic. However, when cells expressing the full-length mVps24p are co-transfected with a mutated form of mVps4p (which is defective in ATP hydrolysis), or when a N-terminal construct of mVps24p is expressed, the class-E cellular phenotype with swollen vacuoles is induced and mVps24p is membrane-associated. Furthermore, the accumulation of the N-terminal mVps24p construct on the swollen endosomal membranes is abrogated when phosphatidylinositol 3,5-bisphosphate synthesis is blocked with wortmannin. These data provide the first direct link between phosphatidylinositol 3,5-bisphosphate and the protein machinery involved in the production of the class-E cellular phenotype. We hypothesize that accumulation of Vps24 on membranes occurs when membrane association (dependent on interaction of phosphatidylinositol 3,5-bisphosphate with the N-terminal domain of the protein) is uncoupled from membrane disassociation (driven by Vps4p). - M Hashimoto, K Nabeta, K MurakamiBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 13 (9) 1531 - 1533 0960-894X 2003/05 [Refereed][Not invited]
3-Trifluoromethylphenyldiazirine based oleic acids derivatives are synthesized to elucidate the functions of specific activation of protein kinase C (PKC) with oleic acid. The synthetic route is based on the alkylation of phenolic derivative with oleic acid equivalent and the post-functionalization. of the compound to achieve radiolabeling. Several compounds have biological activity for PKC with similar efficacy with that of oleic acid. The results indicated that the diaizinyl oleic acid derivatives should be useful to study the specific functions of oleic acid for PKC. (C) 2003 Elsevier Science Ltd. All rights reserved. - M Hashimoto, Y Hatanaka, K NabetaHETEROCYCLES 59 (1) 395 - 398 0385-5414 2003/01 [Refereed][Not invited]
Friedel-Crafts acylation of the aryldiazirine with omega-ester-alpha-acyl halide and successive reduction of the carbonyl group to methylene with triethylsilane and trifluoroacetic acid gave diazirinylated fatty acids. - M Hashimoto, Y Hatanaka, Y Sadakane, K NabetaBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 12 (18) 2507 - 2510 0960-894X 2002/09 [Refereed][Not invited]
An efficient synthesis of tag introducible (3-trifluoromethyl)phenyldiazirine based phenylalanine derivatives is described. Alkylation of a chiral glycine equivalent with a spacer containing (3-trifluoromethyl)phenyldiazirinyl bromides enables us to create photoreactive L-phenylalanine derivatives. After introduction of biotin at the spacer, the biotinylated and photoreactive amino acid was applied for L-amino acid oxidase and incorporated into a substrate binding site. These compounds will be powerful tools not only for photoaffinity labeling to elucidate properties of bioactive peptides but also as trifunctional photophors to introduce a ligand skeleton. (C) 2002 Elsevier Science Ltd. All rights reserved. - M Hashimoto, J Yang, Y Hatanaka, Y Sadakane, K Nakagomi, GD HolmanCHEMICAL & PHARMACEUTICAL BULLETIN 50 (7) 1004 - 1006 0009-2363 2002/07 [Refereed][Not invited]
We have developed two novel 3-phenyl-3-trifluoromethyldiazirinyl bis-glucose derivatives to investigate the properties of the adipocyte glucose transporter GLUT4. These compounds were substituted by electron-withdrawing (iodo and nitro) groups on the aromatic ring of 3-phenyl-3-trifluoromethyldiazirine photophore and were found to be more photosensitive than compounds without such substituents. The compounds were used as inhibitors of insulin-stimulated glucose transport activity in order to assess half-maximal Inhibition or relative affinity values for GLUT4. The affinities were found to be 60-130 times higher than the parent compound D-glucose. Because of the increased photo-reactivity and high affinity these compounds will be useful in studies directed at further elucidation of GLUT4 function. - M Hashimoto, Y Hatanaka, K NabetaBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 12 (1) 89 - 91 0960-894X 2002/01 [Refereed][Not invited]
A versatile synthesis of diazirine-based photoreactive fatty acid analogues is reported. The key step is phenoxy alkylation of diazirine with halo alkyl acid esters. The conditions described will be acceptable for the synthesis of various alkyl-length derivatives. The fatty acid derivatives are acceptors for reverse reactions of sphingolipid ceramide N-deacylase (SCDase), which catalyzes the condensation of psychosine and fatty acids to form photoreactive galactosylceramide. The photoreactive galactosylceramide can also be prepared with chemical synthesis, condensation of psychosine and fatty acid succinimidyl ester, and is recognized with anti-GarCer antibody both before and after irradiation. (C) 2001 Elsevier Science Ltd. All rights reserved. - Synthesis of biotinylated bis(D-glucose) derivatives for glucose transporter photoaffinity labellingM Hashimoto, Y Hatanaka, J Yang, J Dhesi, GD HolmanCARBOHYDRATE RESEARCH 331 (2) 119 - 127 0008-6215 2001/03 [Refereed][Not invited]
New diazirine based bis-glucose derivatives for tagging glucose transporters have been synthesised. These included two biotinylated compounds linked either by an aminocaproate or by a cleavable dithiol link. These compounds have been derivatised via a key skeleton compound that can be easily used for introduction of additional tags. Studies on the erythrocyte glucose transporter (GLUT1) and the insulin-stimulated adipose cell transporter (GLUT-I) have revealed the biotinylated photoreactive bis-glucose compounds are effective labelling reagents, (C) 2001 Elsevier Science Ltd. All rights reserved. - Y Hatanaka, M Ishiguro, M Hashimoto, LN Gastinel, K NakagomiBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 11 (3) 411 - 413 0960-894X 2001/02 [Refereed][Not invited]
A molecular docking study has been performed on the interaction of beta1,4-galactosyltransferase with an acceptor site photoprobe. This is based on an acceptor site peptide fragment which was recently identified by the use of a photoprobe. The present model strongly suggests that the carboxylate group of Asp318 could be involved in the activation of the acceptor sugar 4-OH for the efficient galactosyltransfer. The result also exemplified thar the combination of photoaffinity labeling with crystallography is a powerful method for the detailed structural analysis of ligand-protein complex. (C) 2001 Elsevier Science Ltd. All rights reserved. - M Hashimoto, J Yang, GD HolmanCHEMBIOCHEM 2 (1) 52 - 59 1439-4227 2001/01 [Refereed][Not invited]
Glucose transporters (GLUTs) can be photoaffinity labelled by (diazirinetrifluoroethyl)benzoyl-substituted glucose derivatives and the adduct can be recognised, after detergent solubilisation of membranes, by using streptavidin-based detection systems. However, in intact cells recognition of photolabelled GLUTs by avidin and anti-biotin antibodies only occurs if the bridge between the photoreactive and the biotin moieties has a minimum of 60-70 spacer atoms. We show that a suitably long bridge can be synthesised with a combination of polyethylene glycol and tartarate groups and that introduction of these spacers generates hydrophilic products that can be cleaved with periodate. Introduction of the very long spacers does not appreciably reduce; the affinity of interaction of the probes with the transport system. - M Hashimoto, Y Hatanaka, K NabetaBIOORGANIC & MEDICINAL CHEMISTRY LETTERS 10 (21) 2481 - 2483 0960-894X 2000/11 [Refereed][Not invited]
4-[3-(Trifluoromethyl) diazirinyl] cinnamic acid derivatives were synthesized to elucidate properties of phenylalanine ammonia-lyase (PAL). 2-Methoxy and 2-biotinylated alkoxy compounds have inhibitory activity on the formation of phenylalanine from cinnamic acid. Specific photolabeling of the enzyme was detected using biotinylated derivatives without the use of radioisotopes. The results indicated that the 4-[3-(trifluoromethyl) diazirinyl] skeleton will be a suitable photoreactive compound to elucidate regulation of phenylpropanoid biosynthesis. (C) 2000 Elsevier Science Ltd. All rights reserved. - Gillingham AK, Koumanov F, Hashimoto M, Holman GD, Baldwin SAMembrane Transport 193 - 207 2000 [Refereed][Not invited]
- M Hashimoto, R Hozumi, M Yamamoto, K NabetaPHYTOCHEMISTRY 51 (3) 389 - 394 0031-9422 1999/06 [Refereed][Not invited]
The biosynthesis of 7-hydroxycalamenene using suspension cultured cells of the liverwort, Heteroscyphus planus, is described. The biotransformation of cubenene, but not calamenene, to 7-hydroxycalamenene suggests that it is formed via hydroxylation of the methylene carbon between its unconjugated double bonds. Thus followed by oxidation, thereby explaining the formation of 7-hydroxycalamenene without invoking an NIH shift. (C) 1999 Elsevier Science Ltd. All rights reserved. - M Hashimoto, Y HatanakaCHEMICAL & PHARMACEUTICAL BULLETIN 47 (5) 667 - 671 0009-2363 1999/05 [Refereed][Not invited]
We successfully applied a carbene-generating N-acetylglucosamine derivative carrying a biotinyl group to the radioisotope-free identification of peptides within bovine UDP-galactose: N-acetylglucosamine beta 1,4-galactosyltransferase (GalT, EC 2.4.1.38) catalytic domain. Owing to the low yield of cross-linking, conventional photoaffinity labeling experiments usually encounter a thorny problem in attempting to isolate labeled components from very complex mixtures. A biotin tag introduced with our photoaffinity probe enabled us to separate the photolabeled protein from a large amount of coexisting unlabeled GalT. The introduction of biotin was also useful for the radioisotope-free detection of a labeled protein based on a highly sensitive chemiluminescent technique, We developed a novel poly(vinylidene difluoride) membrane for the identification of labeled peptides in a simple dot blot assay. Using this membrane, we successfully identified biotinyl peptides among a number of HPLC separated fragments derived from the protease digestion of photolabeled GalT proteins. The sequence analysis revealed that the biotin tag was incorporated within a tryptic GalT fragment of Y197-R208. Our approach yields, for the first time, information on the acceptor substrate binding-site fragment in this enzyme, that has been difficult to obtain using other approaches, These data are consistent with previous suggestions concerning the GalT acceptor site and clearly demonstrate the effectiveness of our approach for rapid identification of photolabeled peptides. - K Katoh, K Yamamoto, M Yamamoto, M Hashimoto, K NabetaBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 62 (12) 2480 - 2482 0916-8451 1998/12 [Refereed][Not invited]
NMR analyses of striatol produced by suspension-cultured cells of liverwort, Ptycanthus striatus, in the presence of [2-C-13]- and [4,4-H-2(2)]-MVAs confirmed proton-catalyzed cyclization between the distal and central double bonds in FPP and a concerted series of 1,2-migrations of hydrogen and a methyl group, with subsequent elimination of a proton. - K Nabeta, K Yamamoto, M Hashimoto, H Koshino, K Funatsuki, K KatohCHEMICAL COMMUNICATIONS (14) 1485 - 1486 1359-7345 1998/07 [Refereed][Not invited]
The most uncommon tricyclic sesquiterpenes, kelsoene 1 and prespatane 2, were isolated from cultured cells of liverwort Ptychanthus striatus, and the labelling pattern of kelsoene biosynthesized from exogenous [2-C-13]mevalonate suggested that kelsoene is biosynthesized from germacradienyl cation via alloaromadendranyl cation. - Y Hatanaka, M Hashimoto, Y KanaokaJOURNAL OF THE AMERICAN CHEMICAL SOCIETY 120 (2) 453 - 454 0002-7863 1998/01 [Refereed][Not invited]
- M Hashimoto, Y Kanaoka, Y HatanakaHETEROCYCLES 46 119 - 122 0385-5414 1997/12 [Refereed][Not invited]
We introduce here a novel and simple method for the carbonylation of (alkoxyphenyl)diazirine. 3-(3-Methoxyphenyl)-3-trifluoromethyldiazirine was found to be stable under a typical Friedel-Crafts reaction producing carboxaldehyde derivatives of methoxyphenyldiazirine. The formyl group was easily converted to carboxylic acid, olefin, alcohol, or benzyl bromide providing new derivatives of diazirine photophor in the field of photoaffinity labeling. - Y Hatanaka, M Hashimoto, S Nishihara, H Narimatsu, Y KanaokaCARBOHYDRATE RESEARCH 294 95 - 108 0008-6215 1996/11 [Refereed][Not invited]
A photoreactive N-acetylglucosamine derivative, N-[2-[2-[2-(2-biotinylaminoethoxy)ethoxy]ethoxy]-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-N-4-[2-(acetylamino)-2-deoxy-beta-D-glucopyranosyl]-L-aspartamide (BDGA), was synthesized as a carbene-generating biotinylated probe for UDP-galactose:N-acetylglucosamine beta-(1 --> 4)-galactosyltransferase (GalT). The photoaffinity labeling experiments of bovine GalT with BDGA under various conditions were examined based on the quantitative chemiluminescent detection of the biotinyl residue which was photochemically introduced into the GalT protein. A progressive decrease in the yield of specific photolabeling was observed upon lowering the incubation temperature from 37 degrees C to 20 degrees C or 4 degrees C. The amount of photoincorporation was also decreased when UMP was not included in the incubation mixture, Using a crude protein mixture of recombinant human GalT, a band corresponding to the glutathione S-transferase fusion GalT protein was also specifically visualized. Furthermore, combined use of BDGA photolabeling with an immobilized avidin was found to be effective for the selective retrieval of photolabeled GalT from a reaction mixture containing a large amount of unlabeled GalT protein. The results obtained clearly demonstrate that the covalent biotinylation using the carbene-generating photoaffinity reagent BDGA would be useful for the analysis of acceptor substrate binding sites within the GalT protein. (C) 1996 Elsevier Science Ltd. - Y Hatanaka, M Hashimoto, KIPJ Hidari, Y Sanai, Y Tezuka, Y Nagai, Y KanaokaCHEMICAL & PHARMACEUTICAL BULLETIN 44 (5) 1111 - 1114 0009-2363 1996/05 [Refereed][Not invited]
A new biotinylated lactose derivative bearing a nitro-substituted chromogenic diazirine was synthesized. The biotinyl group within the structure enabled the performance of a convenient assay of GM(3) synthase based on avidin-biotin technology, and the K-m values of this biotinylated photoprobe were determined as 40 and 47 mu M using bovine brain and rat liver Golgi as enzyme sources, respectively. Furthermore, the sialylation of lactosylceramide, a natural acceptor substrate for GM(3) synthase, was competitively inhibited by this synthetic analog. The reagent could be a useful chromogenic photoprobe for GM(3) synthase. - Synthesis of a carbon-linked CMP-NANA analog and its inhibitory effects on GM(3) and GD(3) synthasesY Hatanaka, M Hashimoto, KIPJ Hidari, Y Sanai, Y Nagai, Y KanaokaHETEROCYCLES 43 (3) 531 - 534 0385-5414 1996/03 [Refereed][Not invited]
A carbon-linked analog of cytidine monophospho-N-acetylneuraminic acid (CMP-NANA) was synthesized as the degradation resistant inhibitor for sialyltransferases. The compound is the first example of synthetic CMP-NANA analog that exhibited inhibitory effects on the activity of GM(3) and GD(3) synthases. - Y HATANAKA, M HASHIMOTO, KIPJ HIDARI, Y SANAI, Y NAGAI, Y KANAOKABIOORGANIC & MEDICINAL CHEMISTRY LETTERS 5 (23) 2859 - 2862 0960-894X 1995/12 [Refereed][Not invited]
A new biotinylated lactose derivative bearing a C-14-labeled phenyldiazirine was synthesized. A convenient approach based on avidin-biotin technology was successfully applied for GM(3) synthase assay and the Km value of this biotinylated photoprobe was determined as 180 mu M using rat liver Golgi as the enzyme source. Further characterization revealed that this reagent could be a useful photoprobe for GM(3) synthase. - Y HATANAKA, M HASHIMOTO, H NAKAYAMA, Y KANAOKACHEMICAL & PHARMACEUTICAL BULLETIN 42 (4) 826 - 831 0009-2363 1994/04 [Refereed][Not invited]
3-Phenyl-3-trifluoromethyl-diazirine derivatives with nitro and alkoxy substituents on their aromatic ring have been synthesized as carbene precursors for chromogenic detection of photolabeled products. Photolysis of the diazirines in methanol or cyclohexane gave intermolecular O-H or C-H insertion products, respectively. Spectroscopic properties of the photoproducts are such that detection of photolabeled products may be performed in a spectral region where the absorption due to most biological macromolecules is negligible. A carbon-14 analog of the diazirine was also prepared for microscale detection of labeled products. These nitro-substituted aryl diazirines should be applicable to a wide range of photoaffinity labeling studies, from tracer experiments to preparative isolation of labeled products by HPLC with spectrophotometric detection. - Yasumaru Hatanaka, Makoto Hashimoto, Yuichi KanaokaBioorganic and Medicinal Chemistry 2 (12) 1367 - 1373 0968-0896 1994 [Refereed][Not invited]
The synthesis of a p-[(3-trifluoromethyl)diazirine-3-yl]benzoic acid derivative is described as a new carbene generating heterobifunctional cross-linking reagent. The cross-linker carries a biotin moiety in order to make use of avidin-biotin technology for specific manipulation of cross-linked components. To evaluate the ability of this reagent, the inter-subunit cross-linking of egg-white avidin tetramer was investigated. As a typical application of avidin-biotin technology for cross-linking experiments, a chemiluminescent detection method was examined to identify photobiotinylated components. A cross-linked dimeric product with an apparent molecular mass of 38 kDa was clearly visualized by the combined use of a horseradish peroxidase-streptavidin conjugate and a luminol-based chemiluminescent system. © 1995. - Y HATANAKA, M HASHIMOTO, H KURIHARA, H NAKAYAMA, Y KANAOKAJOURNAL OF ORGANIC CHEMISTRY 59 (2) 383 - 387 0022-3263 1994/01 [Refereed][Not invited]
A series Of simple methods for modifying diazirines bearing an aromatic ring has been accomplished. This first versatile approach involving direct substitution on the aromatic ring of diazirines has been achieved by means of the aromatic thallation of (alkoxyphenyl)diazirines. Introduction of the thallium moiety was successfully followed by nitration, iodination, or palladium-catalyzed carbonylation to give a family of substituted aryldiazirines useful for photolabeling. For instance, diazirines labeled with a nitro group can be detected by spectrophotometric methods, and those labeled with an iodo group can be useful in tracer experiments. The (methoxyphenyl)diazirines were also found to be stable under certain demethylation conditions, thus providing a potential source of diazirines with modifiable phenol hydroxyl groups. By means of this approach, a spacer arm to link diazirines with ligands was readily introduced. Radioactive diazirines labeled with carbon-14 or tritium were also prepared using this method. All the new diazirines were derived from a pair of simple (methoxyphenyl)diazirines. The ease of derivatization of the (alkoxyphenyl)diazirines described here may offer a practical approach to simplify the time-consuming methods currently used for diazirine synthesis. - M HASHIMOTO, H KURIHARA, Y SANAI, K HIDARI, Y NAGAI, Y KANAOKA, Y HATANAKAJOURNAL OF PHARMACOBIO-DYNAMICS 15 (7) S94 - S94 0386-846X 1992/07 [Refereed][Not invited]
- Y HATANAKA, M HASHIMOTO, Y KANAOKAABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 202 105 - ORGN 0065-7727 1991/08 [Refereed][Not invited]
MISC
- 中川詩織, TACHRIM Zetryana Puteri, 崎浜靖子, 橋床泰之, 橋本誠 日本農芸化学会東北支部大会プログラム・講演要旨集 153rd- 84 2018/09/22 [Not refereed][Not invited]
- 佐藤優樹, 橋本誠, 橋床泰之, 崎浜靖子 日本農芸化学会東北支部大会プログラム・講演要旨集 153rd- 48 2018/09/22 [Not refereed][Not invited]
- Yasumaru Hatanaka, Makoto Hashimoto Photoaffinity Labeling for Structural Probing Within Protein 1 -265 2017/09/25 [Not refereed][Not invited]
This book covers the most up-to-date photoaffinity labeling method to tackle the key loop module involved in the binding process of a bioactive small molecule to its host protein. The book introduces rational points for preparing powerful photoaffinity probes, keys for the efficient analysis of labeled products, and recent successful applications for protein probing. Regarding drug design, the unique topics of the book are the special consideration of the crosslinking potential of recent probes and their application of important receptor proteins . This book presents emerging technologies of photoaffinity labeling to readers who are working in the fields of proteomics, molecular recognition, and drug discovery and development. - 橋本誠, WANG Lei, 崎浜靖子, 橋床泰之 日本農芸化学会大会講演要旨集(Web) 2017- ROMBUNNO.3C14a05 (WEB ONLY) 2017/03/05 [Not refereed][Not invited]
- 中北智哉, 石田明子, 小林拓也, 広川貴次, 橋本誠, 三坂巧 日本農芸化学会大会講演要旨集(Web) 2017- 2017
- 中北智哉, 石田明子, 小林拓也, 広川貴次, 橋本誠, 三坂巧 日本味と匂学会誌 24- (3) 2017
- 林寛容, 花井悠介, 橋本誠, 橋床泰之, 崎浜靖子 日本植物学会大会研究発表記録 80th- 168 2016/09/01 [Not refereed][Not invited]
- 林寛容, 布施茜, 羽馬大輔, 橋本誠, 橋床泰之, 崎浜靖子 日本農芸化学会大会講演要旨集(Web) 2016- 2H053 (WEB ONLY) 2016/03/05 [Not refereed][Not invited]
- 吉田卓真, 村井勇太, 橋床泰之, 橋本誠 日本農芸化学会大会講演要旨集(Web) 2016- 3B051 (WEB ONLY) 2016/03/05 [Not refereed][Not invited]
- 花井悠介, 布施茜, 橋床泰之, 橋本誠, 崎浜靖子 日本植物学会大会研究発表記録 79th- 209 2015/09/01 [Not refereed][Not invited]
- Hashimoto Makoto, Misaka Takumi, Ishiguro Masaji, Masuda Katsuyoshi The Japanese journal of taste and smell research 21- (3) 229 -230 2014/12
- 吉田卓真, 村井勇太, LEI Wang, 橋床泰之, 橋本誠 複素環化学討論会講演要旨集 44th- 99 -100 2014/08/25 [Not refereed][Not invited]
- WANG Mengcen, HASHIMOTO Makoto, HASHIDOKO Yasuyuki 講演要旨集 (38) 113 -113 2013/03/14 [Not refereed][Not invited]
- 西塚紘明, 村井勇太, 橋本誠, 橋床泰之 日本農芸化学会大会講演要旨集(Web) 2013- 2A46P06 (WEB ONLY) 2013/03/05 [Not refereed][Not invited]
- 村井勇太, 橋床泰之, 橋本誠 日本農芸化学会北海道支部講演会講演要旨 2012- 17 2012/11/01 [Not refereed][Not invited]
- 大井辰哉, 前田麻起子, 崎浜靖子, 橋本誠, 橋床泰之 日本農芸化学会北海道支部講演会講演要旨 2012- 33 2012/11/01 [Not refereed][Not invited]
- 村井勇太, 橋床泰之, 橋本誠 日本農芸化学会北海道支部講演会講演要旨 2012- 35 2012/11/01 [Not refereed][Not invited]
- 大井辰哉, 前田麻起子, 崎浜靖子, 橋本誠, 橋床泰之 日本農芸化学会大会講演要旨集(Web) 2012- 3A05A15 (WEB ONLY) 2012/03/05 [Not refereed][Not invited]
- 村井勇太, 橋床泰之, 橋本誠 日本農芸化学会大会講演要旨集(Web) 2012- 3A05P02 (WEB ONLY) 2012/03/05 [Not refereed][Not invited]
- 村井勇太, 橋床泰之, 橋本誠 日本農芸化学会大会講演要旨集 2011- 178 2011/03/05 [Not refereed][Not invited]
- 大井辰哉, 前田麻起子, 崎浜靖子, 橋本誠, 橋床泰之 日本農芸化学会大会講演要旨集 2011- 25 2011/03/05 [Not refereed][Not invited]
- 村井勇太, 橋床泰之, 橋本誠 化学系学協会北海道支部冬季研究発表会講演要旨集 2011- 117 2011/02/01 [Not refereed][Not invited]
- 村井勇太, 橋床泰之, 橋本誠 日本農芸化学会東北支部大会プログラム・講演要旨集 145th- 54 2010/09/27 [Not refereed][Not invited]
- Murai Yuta, Hashidoko Yasuyuki, Hashimoto Makoto 講演要旨集 (35) 43 -43 2010/04/21 [Not refereed][Not invited]
- 韓圭鎬, 関川三男, 島田謙一郎, 橋本誠, 橋本直人, 野田高弘, 田中寿, 福島道広 日本農芸化学会大会講演要旨集 2007- 2007
- 福島道広, 島田謙一郎, 橋本誠, 野田高弘 日本農芸化学会北海道支部・日本土壌肥料学会北海道支部・日本生物工学会北日本支部・日本応用糖質科学会北海道支部・北海道農芸化学協会合同学術講演会講演要旨 2005- 2005
Books etc
- Synthesis of Diazirinyl Photophore and Optically Pure Diazirinylphenylalanines for Photoaffinity Labeling.Murai Y, Wang L, Hashimoto M (Joint workPhotoaffinity Labeling for Structural Probing Within Protein)
Elsevier 2017 - Multifunctional Photoprobes for Identification of Ligand Sites Within Biomolecules.Hashimoto MAKOTO (Joint editorPhotoaffinity Labeling for Structural Probing Within Protein.)
Springer 2017 (ISBN: 9784431565697) 1-11
Association Memberships
Research Projects
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific ResearchDate (from‐to) : 2022/04 -2025/03Author : 松浦 英幸, 北岡 直樹, 久保 友彦, 黒田 洋輔, 柏木 純一, 北崎 一義, 橋本 誠
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific ResearchDate (from‐to) : 2017/04 -2020/03Author : Hashimoto MakotoThe detection tags are essential for photoaffinity labeling, which is one of the most reliable methods to elucidate of ligand biological activities. Post-derivatization for the ligand structure of photoaffinity probes are one of the fashion to detect photo labeled components. But isolations of photo labeled components are not easy due to there is no effect methods to isolate the small amounts of labeled components. We found that alpha-aminoketone structure was utilized to cleave specifically by photo-irradiation with different wavelength from photoaffinity labeling. Irradiations with different wavelength is easy to handle to elucidate the ligand-biomolecules relationship.
- Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(C))Date (from‐to) : 2009 -2011Author : Makoto HASHIMOTONovel functional analysis of pinteractions between biomolecules and bioactive compounds with photoreactive trifluoromethylphenyldiazirine containing biotin derivative and immobilized monomeric avidin were examined. New findings are listed below.(1) Synthesis of photoreactive biotinylated compounds(2) Photoaffinity labeling with photoreactive biotinylated ligands on immobilized monomeric avidin.(3) Novel synthesis of biotinylated compounds, which was prepared by Friedel-Crafts reactions.
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific ResearchDate (from‐to) : 2008 -2010Author : KUNIYASU Akihiko, HASHIMOTO MakotoWe developed a hybrid peptide, which induces leukemia cell death associated with autophagy. The mode of cell death induced with this peptide is different from previously recognized apoptosis. Further, the length of peptide sequence was shortened by analyzing active motif of the peptide. The hybrid peptide will be a useful tool for development of novel concept-based anti-leukemia agents.
- Ministry of Education, Culture, Sports, Science and Technology：Grants-in-Aid for Scientific Research(基盤研究(C))Date (from‐to) : 2007 -2008Author : Makoto HASHIMOTOプラチナ含有エチレンジアミン化合物骨格が核酸親和性を持つことを利用し、核酸-生体高分子相互作用解析を行うための新規光アフィニティーラベル用trifluoromethylphenyldiazirine誘導体の合成反応を検討した。プラチナ含有エチレンジアミン化合物骨格に、最終段階でtrifluoromethylphenyldiazirine を導入する方法を選択し、効率よく光反応性基を持つ2価プラチナ化合物の合成に成功し、その性質を検討した。光分解性については、350nm 付近の光照射によりカルベンが発生し標的生体分子との間にクロスリンク反応が半減期は約3分で進行することを確認した。また核酸との相互作用のモデル系としてGMP(グアノシンー1-リン酸)とtrifluoromethylphenyldiazirine 含有プラチナ含有エチレンジアミン化合物の複合体形成を^1H-NMR解析により検討し、期待した通りGMP との相互作用が起きている事を確認した。この事から合成した化合物が、目的とした核酸親和性を持つことが明らかとなり、有機プラチナ化合物に光反応性trifluoromethylphenyldiazirine を修飾してもその親和性に大きな変化が見られない事が明らかとなり、マイクロアレイ解析へ適用するための基礎を確立した。
- 文部科学省：科学研究費補助金(特定領域研究)Date (from‐to) : 2006 -2007Author : 橋本 誠細胞情報伝達系の一つである脂質シグナリングは、その多くが膜蛋白質を介して機能を発現するため、現在頻繁に用いられる機能解析法が適用できない場合があり、新規解析法の確立が望まれている。蛋白質との親和性を解析の基礎とする光アフィニティーラベル法はこの問題解決に有用な手法の一つとなりうる。糖脂質セラミド部は、構造上脂肪酸と長鎖塩基からなり各々の炭素鎖長による生理活性の変化も報告され、基質認識システムの解明が大きな課題となっている。今回の申請において、脂肪酸、長鎖塩基に対する取り扱い容易な安定同位体標識光反応性誘導体の短工程合成の確立、およびそれらを用いたセラミド骨格を構築し、その性質を検討することで、効率的膜蛋白質機能解析法の確立を目指し実験を行った。糖脂質の構成成分であるセラミドは、構造上脂肪酸と長鎖塩基からなり各々の炭素鎖長による生理活性の変化も報告され、基質認識システムの解明が大きな課題となっている。当初筆者らが開発したビオチンー体型ジアジリン化合物を脂肪酸部分に導入したガングリオシド誘導体を調製したが、セラミド認識酵素Sphingolipids ceramide N-deacylase(SCDase)の基質とはならなかった。そこで脂肪酸および長鎖塩基部分への簡便な誘導体化が可能なセラミド誘導体を検討し、セリン誘導体から長鎖塩基末端をアルデヒドとし、アミドおよびシッフ塩基形成による誘導体化可能な化合物を合成した。この化合物は光照射前後とも抗セラミド抗体により天然基質と同様に認識されたことから、セラミド誘導体としてこの新規修飾法は非常に有用であると期待される。
- 文部科学省：科学研究費補助金(若手研究(B))Date (from‐to) : 2004 -2006Author : 橋本 誠光反応性基として利用されるトリフルオロメチルフェニルジアジリン骨格は、光アフィニティーラベルに必要とされる性質を持っているにも関わらず、分子内に必要な置換基を導入するために、その度に多段階反応によるジアジリン骨格形成反応を繰返さなくてはならなかった。そこで、近年進歩の著しい、質量分析計を用いたプロテオーム解析用トリフルオロメチルフェニルジアジリン系光アフィニティーラベルを指向しジアジリン化合物内に安定同位体元素を効率よく導入する反応を検討した。昨年度申請者らによって確立したhypervalentヨウ素化合物利用したトリフルオロメチルフェニルジアジリンのヨウ素化合物に対しPdを用いた炭素伸張反応を検討したところ効率よく反応が進行することを明らかとした。また炭素-ヨウ素結合へのPd炭素の親和性の高さを利用し、ジアジリンの窒素-窒素二重結合存在下選択的なヨウ素-水素交換反応も可能となり、重水素を用いる事で簡便に安定同位体標識化合物合成への道を開拓した。またジアジリン化合物中の炭素-炭素二重結合選択的な接触還元を種々検討し、可溶性触媒であるロジウム錯体のWilkinson触媒を用いる事により目的とする反応を進行させる事に成功した。この合成法により既に報告者が報告しているジアジリンからフリーデルクラフト反応によるアルデヒドへの変換、それに続くWittig反応による増炭時に13-炭素同位体の導入、形成された炭素-炭素二重結合への選択的重水素付加を行う事で質量分析を指向した光反応性誘導体の合成ルートを開発した。
- 文部科学省：科学研究費補助金(特定領域研究)Date (from‐to) : 2005 -2005Author : 橋本 誠細胞情報伝達系の一つである脂質シグナリングは、その多くが膜蛋白質を介して機能を発現するため、現在頻繁に用いられる機能解析法が適用できない場合があり、新規解析法の確立が望まれている。蛋白質との親和性を解析の基礎とする光アフィニティーラベル法はこの問題解決に有用な手法の一つとなりうる。糖脂質セラミド部は、構造上脂肪酸と長鎖塩基からなり各々の炭素鎖長による生理活性の変化も報告され、基質認識システムの解明が大きな課題となっている。今回の申請において、脂肪酸、長鎖塩基に対する取り扱い容易な安定同位体標識光反応性誘導体の短工程合成の確立、およびそれらを用いたセラミド骨格を構築し、その性質を検討することで、効率的膜蛋白質機能解析法の確立を目指し実験を行った。光反応性基としてジアジリンを中心に、実際の生体混合系機能解析に質量分析計を用いることを念頭に入れ、新規に確立したジアジリン化合物への効率的なフリーデルクラフト条件によるアシル化後、カルボニル基の還元時に重水素化試薬を用いることで簡便に重水素の導入に成功した。この光反応性試薬を用いた機能解析において、光ラベル蛋白質が一定の割合で安定同位体元素を含む事になり、質量スペクトル上でラベルされていない蛋白質との区別が格段に容易になると期待される。また、光ラベルされた生体高分子選択的な有用官能基導入法の検討も行い、シッフ塩基形成反応および分子内Staudinger反応がこの目的に利用可能であることを明らかとした。
- 文部科学省：科学研究費補助金(奨励研究(A))Date (from‐to) : 2000 -2001Author : 橋本 誠Sphigolipid ceramide N-deacylaseは糖脂質の脂質部分を認識し長鎖塩基と脂肪酸に分解する酵素であり、その疎水部分の認識メカニズムは、非常に興味深い。申請者は、昨年度この酵素の機能解析用試薬の開発として、フェノール性水酸基のアルキル化を鍵反応とした、同一条件により種々の炭素鎖が導入できる光反応性脂肪酸誘導体の合成法を確立した。この方法では酸素原子が脂肪酸末端部分に入ってしまうことから、今年度は、酸素原子を介さない導入法検討を行った。大量合成(0.5モルスケール)可能な光反応性基ジアジリンのベンゼン環上に直接Friedel-Craftアシル化を行い、生成したアリールケトンの還元を種々の試薬を用いて検討したところ、トリエチルシランートリフルオロ酢酸系による還元で酸素原子を介さない新規光反応性脂肪酸誘導体の合成に成功した。光反応性ジアジリン誘導体においてカルボニル基の炭化水素への還元の成功は初めての例である。また、昨年合成に成功した光反応性ビオチン化セラミドをSphigolipid ceramide N-deacylaseの光アフィニティーラベルに適用した。その結果光照射により標的蛋白質へのビオチン化に成功し、天然基質であるガングリオシドの存在により阻害された。このことから、この試薬が酵素活性中心に天然基質と同様に特異的な認識をうけていることが明かとなった。このラベル蛋白の酵素消化を行い断片化することで8000前後のペプチドへとすることができた。
- 新規光アフィニティーラベル法の開発科学研究費補助金Date (from‐to) : 1993
- Application of novel photoaffinity labelingGrant-in-Aid for Scientific ResearchDate (from‐to) : 1993