研究者データベース

長堀 紀子(ナガホリ ノリコ)
ダイバーシティ・インクルージョン推進本部
特任教授

基本情報

所属

  • ダイバーシティ・インクルージョン推進本部

職名

  • 特任教授

学位

  • 博士(理学)(北海道大学)

ホームページURL

J-Global ID

研究キーワード

  • キャリア開発   女性研究者   人材育成   生体関連化学   生物分子科学   分子イメージング   糖鎖   量子ドット   ナノ微粒子   glycobiology   chemical biology   carbohydrate chemistry   molecular life science   bio-organic chemistry   

研究分野

  • ナノテク・材料 / 生体化学
  • ナノテク・材料 / 生物分子化学
  • ナノテク・材料 / ナノバイオサイエンス
  • ナノテク・材料 / ナノ材料科学

職歴

  • 2020年04月 - 現在 北海道大学 人材育成本部 ダイバーシティ研究環境推進室 特任教授
  • 2015年04月 - 2020年03月 北海道大学 人材育成本部 女性研究者支援室 特任准教授
  • 2013年04月 - 2015年03月 経済産業省 北海道経済産業局地域経済部バイオ産業課 課長補佐
  • 2008年10月 - 2013年03月 北海道大学 大学院先端生命科学研究院 特任助教
  • 2006年04月 - 2008年09月 北海道大学 大学院先端生命科学研究院 特任助手
  • 2003年10月 - 2006年03月 北海道大学 大学院理学研究院 寄附講座教員
  • 2003年04月 - 2003年09月 一般財団法人バイオインダストリー協会 博士研究員
  • 2003年01月 - 2003年03月 株式会社生物有機化学研究所 博士研究員

学歴

  • 1999年04月 - 2002年12月   北海道大学   大学院理学研究科   博士課程
  • 2000年04月 - 2001年06月   ジョンズホプキンス大学   生物学科
  • 1997年04月 - 1999年03月   北海道大学   大学院理学研究科   修士課程
  • 1993年04月 - 1997年03月   北海道大学   理学部生物科学科

所属学協会

  • 研究・イノベーション学会   日本女性科学者の会   糖質学会   生化学会   高分子学会   

研究活動情報

論文

  • Feng F, Sakoda Y, Ohyanagi T, Nagahori N, Shibuya H, Okamastu M, Miura N, Kida H, Nishimura S
    Antiviral chemistry & chemotherapy 23 59 - 65 2 2013年05月 [査読有り][通常論文]
  • Feng F, Sakoda Y, Ohyanagi T, Nagahori N, Shibuya H, Okamastu M, Miura N, Kida H, Nishimura SI
    Antiviral therapy 2013年02月 [査読有り][通常論文]
  • Masatoshi Okamatsu, Fei Feng, Tatsuya Ohyanagi, Noriko Nagahori, Kazuhiko Someya, Yoshihiro Sakoda, Nobuaki Miura, Shin-Ichiro Nishimura, Hiroshi Kida
    JOURNAL OF VIROLOGICAL METHODS 187 2 390 - 394 2013年02月 [査読有り][通常論文]
     
    Attachment of influenza virus to susceptible cells is mediated by viral protein hemagglutinin (HA), which recognizes cell surface glycoconjugates that terminate in alpha-sialosides. To develop anti-influenza drugs based on inhibition of HA-mediated infection, novel fluorescent nanoparticles displaying multiple biantennary N-glycan chains with alpha-sialosides (A2-PC-QDs) that have high affinity for the HA were designed and constructed. The A2-PC-QDs enabled an easy and efficient fluorescence polarization (FP) assay for detection of interaction with the HA and competitive inhibition even by small molecule compounds against A2-PC-QDs-HA binding. The quantum dot (QD)-based FP assay established in the present study is a useful tool for high-throughput screening and to accelerate the development of novel and more effective blockers of the viral attachment of influenza virus. (C) 2012 Elsevier B.V. All rights reserved.
  • Noriko Nagahori, Tadashi Yamashita, Maho Amano, Shin-Ichiro Nishimura
    CHEMBIOCHEM 14 1 73 - 82 2013年01月 [査読有り][通常論文]
     
    The structural and clinical significance of cellular glycoproteins and glycosphingolipids (GSLs) are often separately discussed. Considering the biosynthetic pathway of glycoconjugates, glycans of cell-surface glycoproteins and GSLs might partially share functions in maintaining cellular homeostatis. The purpose of this study is to establish a general and comprehensive glycomics protocol for cellular GSLs and N-glycans of glycoproteins. To test the feasibility of a glycoblotting-based protocol, whole glycans released both from GSLs and glycoproteins were profiled concurrently by using GM3 synthase-deficient mouse embryonic fibroblast GM3(-/-). GM3(-/-) cells did not synthesize GM3 or any downstream product of GM3 synthase. Instead, expression levels of o-series gangliosides involving GM1-b and GD1-alpha increased dramatically, whereas a-/b-series gangliosides were predominantly detected in wild-type (WT) cells. We also discovered that glycoprotein N-glycan profiles of GM3(-/-) cells are significantly altered as compared to WT cells, although GM3 synthase is responsible only for GSLs synthesis and is not associated with glycoprotein N-glycan biosynthesis. The present approach allows for high-throughput profiling of cellular glycomes enriched by different classes of glycoconjugates, and our results demonstrated that gene knockout of the enzymes responsible for GSL biosynthesis significantly influences the N-glycans of glycoproteins.
  • Noriko Nagahori, Makiyo Uchida, Masataka Kinjo, Tadashi Yamashita
    CURRENT PHARMACEUTICAL BIOTECHNOLOGY 13 14 2612 - 2616 2012年11月 [査読有り][通常論文]
     
    Functional analysis of carbohydrates is needed to understand the initial interface between membranes and the outer world. For this analysis we need individual protocols such as a method to modify the surfaces of nanoparticles with a variety of carbohydrates effectively and exhaustively, to synthesize an oligosaccharide on each particle's surface by chemical or enzymatic sugar elongation reaction, and to analyze the binding properties of carbohydrates. In this article, we describe the basic strategies for scooping up proteins from crude sample mixtures via interaction with carbohydrates. This approach was used to identify proteins that interacted with GM2, a ganglioside that is abundant on the surfaces of human lung cancer cells.
  • Tatsuya Ohyanagi, Noriko Nagahori, Ken Shimawaki, Hiroshi Hinou, Tadashi Yamashita, Akira Sasaki, Takashi Jin, Toshihiko Iwanaga, Masataka Kinjo, Shin-Ichiro Nishimura
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 133 32 12507 - 12517 2011年08月 [査読有り][通常論文]
     
    Glycans are expected to be one of the potential signal molecules for controlling drug targeting/delivery or long-term circulation of biopharmaceuticals. However, the effect of the carbohydrates of artificially glycosylated derivatives on in vivo dynamic distribution profiles after intravenous injection of model animals remains unclear due to the lack of standardized methodology and a suitable platform. We report herein an efficient and versatile method for the preparation of multifunctional quantum dots (QDs) displaying common synthetic glycosides with excellent solubility and long-term stability in aqueous solution without loss of quantum yields. Combined use of an aminooxy-terminated thiol derivative, 11,11'-dithio bis[undec-11-yl 12-(aminooxyacetyl)amino hexa(ethyleneglycol)], and a phosphorylcholine derivative, 11-mercaptoundecylphosphorylcholine, provided QDs with novel functions for the chemical ligation of ketone-functionalized compounds and the prevention of nonspecific protein adsorption concurrently. In vivo near-infrared (NIR) fluorescence imaging of phosphorylcholine self-assembled monolayer (SAM)-coated QDs displaying various simple sugars (glyco-PC-QDs) after administration into the tail vein of the mouse revealed that distinct long-term delocalization over 2 h can be achieved in cases of QDs modified with alpha-sialic acid residue (Neu5Ac-PC-QDs) and control PC-QDs, while QDs bearing other common sugars, such as alpha-glucose (Glc-PC-QDs), alpha-mannose (Man-PC-QDs), alpha-fucose (Fuc-PC-QDs), lactose (Lac-PC-QDs), beta-glucuronic acid (GlcA-PC-QDs), N-acetyl-beta-D-glucosamine (GlcNAc-PC-QDs), and N-acetyl-beta-D-galactosamine (GalNAc-PC-QDs) residues, accumulated rapidly (5-10 min) in the liver. Sequential enzymatic modifications of GlcNAc-PC-QDs gave Gal beta 1,4GlcNAc-PC-QDs (LacNAc-PC-QDs), Gal beta 1,4(Fuc alpha 1,3)GlcNAc-PC-QDs (Le(x)-PC-QDs), Neu5Ac alpha 2,3Gal beta 1,4GlcNAc-PC-QDs (sialyl LacNAc-PC-QDs), and Neu5Ac alpha 2,3Gal beta 1,4(Fuc alpha 1,3)GlcNAc-PC-QDs (sialyl Le(x)-PC-QDs) in quantitative yield as monitored by direct matrix-assisted laser desorption ionization time-of-flight mass spectrometry analyses. Live animal imaging uncovered for the first time that Le(x)-PC-QDs also distributed rapidly in the liver after intravenous injection and almost quenched over 1 h in similar profiles to those of LacNAc-PC-QDs and Lac-PC-QDs. On the other hand, sialyl LacNAc-PC-QDs and sialyl Le(x)-PC-QDs were still retained stably in the whole body after 2 h, while they showed significantly different in vivo dynamics in the tissue distribution, suggesting that structure/sequence of the neighboring sugar residues in the individual sialyl oligosaccharides might influence the final organ-specific distribution. The present results clearly visualize the evidence of an essential role of the terminal sialic acid residue(s) for achieving prolonged in vivo lifetime and biodistribution of various glyco-PC-QDs as a novel class of functional platforms for nanomaterial-based drug targeting/delivery. A standardized protocol using multifunctional PC-QDs should facilitate live animal imaging of ligand-displayed QDs using versatile NIR fluorescence photometry without influence of size-dependent accumulation/excretion pathway for nanoparticles (e.g., viruses) >10 nm in hydrodynamic diameter by the liver.
  • Yoshiaki Miura, Kentaro Kato, Yasuhiro Takegawa, Masaki Kurogochi, Jun-ichi Furukawa, Yasuro Shinohara, Noriko Nagahori, Maho Amano, Hiroshi Hinou, Shin-Ichiro Nishimura
    ANALYTICAL CHEMISTRY 82 24 10021 - 10029 2010年12月 [査読有り][通常論文]
     
    Glycoblotting, high throughput method for N-glycan enrichment analysis based on the specific chemical ligation between aminooxy/hyclrazide-polymers/solids and reducing N-glycans released from whole serum and cellular glycoproteins, was proved to be feasible for selective enrichment analysis of O-glycans of common (mucin) glycoproteins. We established a standard protocol of glycoblotting-based O-glycomics in combination with nonenzymatic chemical treatment to release reducing O-glycans predominantly from various glycoprotein samples. It was demonstrated that the nonreductive condition employing a simple ammonium salt, ammonium carbamate, made glycoblotting-based enrichment analysis of O-glycans possible without significant loss or unfavorable side reactions. A general workflow of glycoblotting using a hydrazide bead (BlotGlyco H), on-bead chemical manipulations, and subsequent mass spectrometry allowed for rapid O-glycomics of human milk osteopontin (OPN) and urinary MUC1 glycoproteins purified from healthy donors in a quantitative manner. It was revealed that structures of O-glycans in human milk OPN were varied with habitual fucosylation and N-acetyllactosamine units. It was also suggested that purified human urinary MUC1 was modified preferentially by sialylated O-glycans (94% of total) with 7:3 ratio of core 1 to core 2 type O-glycans. Versatility of the present strategy is evident because this method was proved to be suited for the enrichment analysis of general biological and clinical samples such as human serum and urine, cultured human cancer cells, and formalin-fixed paraffin-embedded tissue sections. It is our belief that the present protocols would greatly accelerate discovery of disease-relevant O-glycans as potential biomarkers.
  • Noriko Nagahori, Midori Abe, Shin-Ichiro Nishimura
    BIOCHEMISTRY 48 3 583 - 594 2009年01月 [査読有り][通常論文]
     
    Glycosphingolipids (GSLs) synthesized in Golgi apparatus by sequential transfer of sugar residues to a ceramide lipid anchor are ubiquitously distributing on vertebrate plasma membranes. A standardized method allowing for high-throughput structural profiling and functional characterization of living cell surface GSLs is of growing importance because they function as crucial signal transduction molecules in various processes of dynamic cellular recognitions. However, methods are not available for amplification of GSLs, while the genomic scale PCR amplification permits large-scale mammalian proteomic analysis. Here we communicate such an approach to a novel "omics", namely, glycosphin-golipidomics based on the "glycoblotting" method. The method, which involves selective ozonolysis of the C-C double bond in the ceramide moiety and subsequent enrichment of generated GSL aldehydes by chemical ligation using an aminooxy-functionalized gold nanoparticle (aoGNP) should be of widespread utility for identifying and characterizing whole GSLs present in the living cell surfaces. The present protocol using glycoblotting permitted MALDI-TOFMS-based high-throughput structural profiling of mouse brain gangliosides such as GM1, GD1a/GD1b, and GT1b for adult or GD3 in the case for the embryonic mouse. When mouse melanoma B16 cells were subjected to this protocol, it was demonstrated that gangliosides enriched from the plasma membranes are the only GM3 bearing microheteogeneity in the structure of the N-acyl chain. Surface plasmon resonance analysis revealed that aoGNP displaying whole GSLs blotted from mouse B 16 melanoma cell surfaces can be used directly for monitoring the specific interaction with the self-assembled monolayer (SAM) of Gg3Cer (gangliotriaosylceramide). Our results indicate that GSL-selective enrichment onto aoGNP from living cell surfaces allows for rapid reconstruction of plasma membrane models mimicking the intact GSL microdomain feasible for further structural and functional characterization.
  • Hiroaki Nakagawa, Miki Ohira, Shunji Hayashi, Shigeaki Abe, Shin Saito, Noriko Nagahori, Kenji Monde, Yasuro Shinohara, Naoki Fujitani, Hirosato Kondo, Shin-Ichi Akiyama, Akira Nakagawara, Shin-Ichiro Nishimura
    CANCER LETTERS 270 2 295 - 301 2008年11月 [査読有り][通常論文]
     
    Cisplatin, cis-diamineplatinum-(II) dichloride (CDDP), is one of the most common and valuable chemotherapeutic reagents for various cancers. However, it is well known that tumor cells gain acquired or intrinsic resistance to treatment by this anti-cancer reagent. In spite of extensive efforts using genetic and proteomic approaches, the mechanism underlying CDDP resistance remains unclear. In the present study, we report drastic structural changes in the N-glycans of glycoproteins in CDDP-resistant tumor cells (the KCP-4 cell line obtained from KB-3-1 human carcinoma cells). It was suggested that the CDDP-resistant cells exhibited an increase in one of the high-mannose-type glycans, particularly M8.1. This N-glycan is well known as a tag for the transport of unfolded protein from the endoplasmic reticulum to the lysosome, a process known as endoplasmic reticulum-associated degradation (ERAD) system. The revertant cells (KCP-4R) obtained from the KCP-4 cell line showed almost the same glycoform profile as that of the parental cells, suggesting that N-glycan biosynthesis in tumor cells clearly corresponds to the alteration in the sensitivity against CDDP. Gene expression analysis using a cDNA microarray showed a decrease in the expression of major histocompatibility complex (MHC) proteins in the resistant cells. MHC proteins form a complex with lysosome-degradated proteins and are presented on the cell surface. These results suggest that CDDP tolerance in KCP-4 cells is caused by a defect in the ERAD system. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
  • Hiroki Shimizu, Masahiro Sakamoto, Noriko Nagahori, Shin-Ichiro Nishimura
    TETRAHEDRON 63 11 2418 - 2425 2007年03月 [査読有り][通常論文]
     
    A new reaction for carbohydrate elongation for synthesis of oligosaccharide using gold colloidal nanoparticles (GCNPs) has been developed. The gold core in this colloidal phase synthesis was prepared by a reduction of tetrachloroauric acid with 30,31-dithia-3,6,9,12,15,18,43,46,49,52,55,58-dodecaoxa-1,60-hexacontanediol. The presented alkanethionyl oligomeric ethylene glycol worked as a stabilizer of GCNPs and as a linker in chemical elongations of carbohydrates. This colloidal phase synthesis has several advantages such as (1) remnants of reagents and glycosyl donors in each reaction could be easily removed by ultrafiltration or gel filtration column chromatography, (2) further purifications are not required, and (3) the reactions can be monitored by MALDI-TOF MS directly without any pretreatment. In fact, we have successfully synthesized lactose derivative on GCNPs and will report these results in this paper. (c) 2007 Elsevier Ltd. All rights reserved.
  • Yoshiaki Miura, Yasuro Shinohara, Jun-ichi Furukawa, Noriko Nagahori, Shin-ichiro Nishimurara
    CHEMISTRY-A EUROPEAN JOURNAL 13 17 4797 - 4804 2007年 [査読有り][通常論文]
     
    A rapid and quantitative method for solid-phase methyl esterification of carboxy groups of various sialylated oligosaccharides has been established. The method employed a triazene derivative, 3-methyl-1-p-tolyltriazene, for facile derivatization of oligosaccharides immobilized onto general solid supports such as Affi-Gel Hz and gold colloidal nanoparticles in a multi-well plate. The workflow protocol was optimized for the solid-phase processing of captured sialylated/unsialylated oligosaccharides separated from crude sample mixtures by chemical ligation. From tryptic and/or PNGase F-digest mixtures of glycoproteins, purification by chemoselective immobilization, esterification and recovery were achieved in the same well of the filter plate within three hours when used in conjunction with "glycoblotting technology" (SA. Nishimura, K. Niikura, M. Kurogochi, T Matsushita, M. Fumoto, H. Hinou, R. Kamitani, H. Nakagawa, K. Deguchi, N. Miura, K. Monde, H. Kondo, High-throughput protein glycomics: Combined use of chemoselective glycoblotting and MALDI-TOF/TOF mass spectrometry: Angew. Chem. 2005, 117, 93-98; Angew. Chem. Int. Ed. 2005, 44, 9196). The recovered materials were directly applicable to subsequent characterization by mass spectrometric techniques such as MALDI-TOF for large-scale glycomics of both neutral and sialylated oligosaccharides. On-bead/on-gold nanoparticle derivatization of glycans containing sialic acids allowed rapid and quantitative glycoform profiling by MALDI-TOF MS with reflector and positive ion mode. In addition to its simplicity and speed, the method eliminates the use of unfavorable halogenated solvents such as chloroform and dichloromethane or volatile solvents such as diethyl ether and hexane, resulting in a practical and green chemical method for automated robotic adaptation.
  • Tomohiro Onodera, Kenichi Niikura, Norimasa Iwasaki, Noriko Nagahori, Hideyuki Shimaoka, Ryusuke Kamitani, Tokifumi Majima, Akio Minami, Shin-Ichiro Nishimura
    BIOMACROMOLECULES 7 11 2949 - 2955 2006年11月 [査読有り][通常論文]
     
    We synthesized an aminooxyl polymer that is reactive with the reduced end of carbohydrates using our sugar-displaying approach. The carbohydrates were easily immobilized on the polymer film (glycoblotting film) by simple immersion in a in sugar solution through stable oxime bond. The in vitro behaviors of human fibroblasts on the carbohydrate-coated surface were investigated. The adhesion of human fibroblasts on the cellobiose- and cellotriose-coated surfaces was much greater than on the other coated surfaces and the noncoated surface. This result indicated that simple structural differences in carbohydrates induced biological changes in human cells, especially cell adhesion. Our approach provides a high-throughput assay system for carbohydrate-related cell adhesion and proliferation.
  • Noriko Nagahori, Shin-Ichiro Nishimura
    CHEMISTRY-A EUROPEAN JOURNAL 12 25 6478 - 6485 2006年08月 [査読有り][通常論文]
     
    A simple and efficient assay for glycosyltransferase activity on gold colloidal nanoparticles (GCNPs) by using laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) is demonstrated by the enzymatic synthesis of the Lewis X trisaccharide on GCNPs containing GlcNAc residues. GCNPs containing multivalent sugars were well dispersed in aqueous solution and proved to be excellent acceptor substrates for the glycosyltransferase reaction. Direct LDI-TOF MS analysis of these GCNPs provided the ion peaks of the sugar derivatives, chemisorbed through S-Au linkages onto the GCNPs, even in the presence of contaminants such as proteins and salts. Thus, it enabled the rapid and direct detection of the enzymatic reaction on the GCNPs by subjecting a small amount (0.15 mu L) of the reaction mixture to MS analysis without purification. Subsequent MS/MS analyses (LDI-LIFT-TOF/TOF method) of the product-carrying GCNPs enabled the structures of the sugar derivatives that had been constructed on the GCNPs by enzymatic glycosylation to be determined. A quantitative inhibition assay for glycosyltransferase by using LDI-TOF MS analysis on the GCNPs was demonstrated by using uridine 5'-diphosphate (UDP) as the inhibitor. This simple assay was then applied to the detection of the enzymatic activity of a crude cell extract of Escherichia coli, which produces Neisseria meningitidis beta-1,4-galactosyltransferase (beta-1,4-GalT). In this case, the GCNPs were roughly purified by means of ultrafiltration to remove the buffer and detergents before MS analysis. That the GCNPs are dissolved in solution in the reaction medium but are solid in the purification process is greatly advantageous for the simple and efficient detection of enzymatic activity in crude biological samples. Thus, GCNPs containing a variety of biomolecules may become a versatile and efficient tool for the rapid and direct monitoring of metabolism (metabolomics) in living cells when combined with LDI-TOF MS analysis.
  • K Takaya, N Nagahori, M Kurogochi, T Furuike, N Miura, K Monde, YC Lee, SI Nishimura
    JOURNAL OF MEDICINAL CHEMISTRY 48 19 6054 - 6065 2005年09月 [査読有り][通常論文]
     
    An affinity labeling reagent, uridine 5'-(6-amino-{2-[(7-bromomethyl-2-naphthyl)methoxy-carbonylmethoxy]ethoxy}acetyl-6-deoxy-alpha-D-galactopyranosyl) diphosphate (1a), was designed on the basis of 3D docking simulation and synthesized to investigate the functional role of Trp310 residue located in the small loop near the active site of human recombinant galactosyltransferase (beta GalT-1). Mass spectrometric analysis revealed that the Trp310 residue of beta GalT1 can be selectively modified with the naphthylmethyl group of compound la at the C-3 position of the indole ring. This result motivated us to synthesize novel uridine-5'-diphosphogalactose (UDP-Gal) analogues as candidates for mechanism-based inhibitors for beta GalT-1. We found that uridine 5'-(6-O-[10-(2-naphthyl)-3,6,9-trioxadecanyl]-alpha-D-galactopyranosyl) diphosphate (2) is the strongest inhibitor (K-i = 1.86 mu M) against UDP-Gal (K-m = 4.91 mu M) among compounds reported previously. A cold spray ionization time-of-flight mass spectrometry study demonstrated that the complex of this inhibitor and beta GalT-1 cannot interact with an acceptor substrate in the presence of Mn2+.
  • SI Nishimura, N Nagahori, K Takaya, Y Tachibana, N Miura, K Monde
    ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 44 4 571 - 575 2005年 [査読有り][通常論文]
  • SI Nishimura, N Nagahori, R Sadamoto, K Monde, K Niikura
    SYNTHESIS OF CARBOHYDRATES THROUGH BIOTECHNOLOGY 873 113 - 124 2004年 [査読有り][通常論文]
     
    Enzymatic synthesis is potential method for the construction of glycoconjugates as well as conventional chemical synthesis. Use of glycosyltransferases in the synthetic schemes has accelerated practical synthesis of oligosaccharides and related compounds. However, there is no systematic approach for establishing "automated glycosynthesizer" based on the combined chemical and enzymatic strategy. We have found that water-soluble glycopolymers bearing multivalent sugars become excellent glycosyl acceptor substrates of glycosyltransferases. Affinity of enzymes with multivalent glycosyl acceptors was drastically enhanced by polymeric sugar-cluster effect. Some designed linkers that can be recognized by specific enzyme permitted release of products from polymer supports under mild and selective conditions. By employing these water-soluble primers with some engineered glycosyltransferases, we succeeded to produce "artificial Golgi apparatus", an automatic glycosynthesizer controlled by computer. In this chapter, our recent approach for direct monitoring of sugar -elongation reactions by using surface plasmon resonance (SPR) method will be described, since direct and real time monitoring of enzymatic carbohydrate synthesis is strongly required for materializing practically usable artificial Golgi apparatus. (C) 2004 American Chemical Society.
  • K Niikura, N Osuga, N Nagahori, R Sadamoto, M Shiono, N Iwasaki, K Monde, A Minami, SI Nishimura
    POLYMER JOURNAL 36 3 209 - 218 2004年 [査読有り][通常論文]
     
    We prepared sugar-displayed fluorescent nanoparticles using photopolyinerization of the vesicles of diacetylene-containing glycolipids. After photopolymerization, the nanoparticles exhibited fluorescent emission at 400-600 nm upon excitation at 380 nm. The binding of sugar-recognizing proteins (lectins) onto the fluorecent nanoparticles induced changes in fluorescence. The fluorescent intensity of the nanoparticles decreased with an increase in lectin concentration. On the contrary, the enzymatic release of oligosaccharides from the glyconanoparticles gave an increase in fluorescence. Using a phosphatidylcholine-type lipid as the matrix lipid of the nanoparticles, the non-specific adsorption of lectins on the surface was drastically restricted, leading to the generation of a specific response to the target proteins.
  • N Nagahori, K Niikura, R Sadamoto, M Taniguchi, A Yamagishi, K Monde, SI Nishimura
    ADVANCED SYNTHESIS & CATALYSIS 345 6-7 729 - 734 2003年06月 [査読有り][通常論文]
     
    beta(1-->4) Galactosyltransferase expressed as a fusion protein with maltose binding protein (MBP-GalT) was displayed specifically on a Langmuir-Blodgett (LB) membrane prepared by photopolymerization of maltotriose-carrying glycolipid (1) with 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (2). The catalytic activity of MBP-GalT on the LB film was directly monitored by the surface plasmon resonance (SPR) method using a GlcNAc-carrying water-soluble polymer (3) as an acceptor substrate. Highly sensitive sigmoidal-type signals were obtained upon the addition of the acceptor substrate in the presence of the donor substrate, UDP-galactose (UDP-Gal), while the binding of 3 was not detected in the absence of UDP-Gal. The intensities of the signals were dependent on the amount of immobilized MBP-GalT on the LB film, which was estimated from the images obtained by atomic force microscope (AFM).
  • N Nagahori, K Niikura, R Sadamoto, K Mondea, SI Nishimura
    AUSTRALIAN JOURNAL OF CHEMISTRY 56 6 567 - 576 2003年 [査読有り][通常論文]
     
    Photopolymerizable glycolipids incorporating ceramide- or amido-type linkers and able to form stable monolayers were efficiently synthesized by chemical and enzymatic methods. Glycolipid polymer films served as platforms for the immobilization of proteins through specific carbohydrate - protein interactions at the air - water interface. Carbohydrate-binding proteins deposited on the glycolipid film were observed by atomic force microscopy, which showed varying submicron-sized protein patterns such as dendrites, dots, and networks, depending on the lipid structure, membrane preparation process, and sugar density of the membrane. Surface plasmon resonance measurement confirmed that the subunit-type lectins immobilized on the glycolipid membranes exhibited the ability to interact specifically with carbohydrate ligands by using unoccupied binding sites.
  • N Nagahori, RT Lee, S Nishimura, D Page, R Roy, YC Lee
    CHEMBIOCHEM 3 9 836 - 844 2002年09月 [査読有り][通常論文]
     
    The inhibitory potencies of a number of mannosides, di- and trivalent mannosides, a set of mannose-terminating dendrimers, and five types of mannose-bearing neoglycoproteins were determined by using a binding assay that measures the binding of I-125-labeled, highly mannosylated neoglycoprotein to a type 1 fimbriated Escherichia coli (K72) strain In suspension. The IC50 values (the concentration of inhibitor that causes 50 % reduction-in the bound I-125-ligand to E. coli) obtained by this method were much lower than the equivalent values obtain hemagglutination or in assays that involve microplate immobilization. Two important factors that strongly influence the affinity to E. coli adhesin are: 1) the presence of an alpha-oriented aglycon that has a long aliphatic chain or an aromatic group immediately next to the glycosyl oxygen, and 2) the presence of multiple mannosyl residues that can span a distance of 20 nm or longer on a relatively structure. The two best inhibitors, which ore a highly mannosylated neoglycoprotein with the longest linking arm between a mannose and protein amino group and the largest mannosylated dendrimer (fourth generation), exhibited sub-nM IC50 values.
  • N. Nagahori, S. I. Nishimura
    Biomacromolecules 2 1 22 - 24 2001年 [査読有り][通常論文]

書籍

  • 子どもの文化「北海道大学における子育て支援の取組ー地域の事業者としてー」
    長堀 紀子 
    一般財団法人文民教育協会 子どもの文化研究所 2017年 p2-p11,2月号
  • 椎野 若菜, 的場 澄人, 中川 千草, 永塚 尚子, 國弘 暁子, 新ヶ江 章友, 長堀 紀子, 久世 濃子, 杉田 映理, 酒井 麻衣, 四方 篝, 石井 美保, 菊地 滋夫, 菊地 紀久恵, 三谷 曜子 
    古今書院 2016年 (ISBN: 9784772271332)
  • 化学工業「蛍光相互相関分光法を用いた分子間相互作用解析の応用」
    長堀 紀子, 金城 政孝 (担当:共著)
    2012年 P18-23,Vol.63,No1
  • 「糖鎖ケミカルバイオロジー」蛋白質核酸酵素
    長堀 紀子, 西村 紳一郎 (担当:共著)
    共立出版 2007年10月 Vol.152,Mo.13,1742-1750
  • バイオとナノの融合Ⅱ−新生命科学の応用,第Ⅱ部 最新の科学で創薬「糖鎖ナノケミカルバイオロジー」
    長堀 紀子, 西村 紳一郎 (担当:共著)
    北海道大学出版会 2007年
  • “Glycopolymers” Multivalent presentation, in Comprehensive Glycoscience
    Nagahori Noriko, Nisimura Sinichirou (担当:共著)
    Elsevier 2007年 453-476
  • "Glyconanotechnology" in Nanotechnology in Carbohydrate Chemistry
    Nagahori Noriko, Nisimura Sinichirou (担当:共著)
    Transworld Research Network 2006年 149-166
  • “Direct monitoring of Enzymatic Reaction by Using Glyco-nanoassembly” in BOTTOM UP NANO FABRICATION
    Nagahori Noriko, Nisimura Sinichirou (担当:共著)
    American Scientific Publishers 2006年
  • “Direct Observation of Biomolecular Complexes by Cold-Spray Iionization Time-of-Flight Mass Spectrometry”
    Nagahori Noriko, Nisimura Sinichirou (担当:共著)
    JEOL News 2006年 vol 41, No1, 35-39
  • Cold-Spray Ionization (CSI)-TOF MSによる生体分子間相互作用解析
    長堀 紀子, 西村 紳一郎 
    日本電子ニュース 2005年 Vol 37, 2-5
  • "Artificial Golgi Apparatus: Direct Monitoring of Glycosylation Reaction on Automated Glycosynthesizer" ACS SYMPOSIUM SERIES 873, Synthesis of Carbohydrates through Biotechnology
    Nagahori Noriko, Nisimura Sinichirou, R. Sadamoto, K. Monde, K. Niikura 
    2004年 Chapter 8, 113-124
  • 化学フロンティア13「糖鎖ナノテクノロジー」
    長堀 紀子, 西村 紳一郎, 新倉 謙一 (担当:共著)
    化学同人 2004年 p24-36
  • バイオチップの最新技術と応用、第3章、糖鎖チップの応用技術「糖鎖合成技術の開発」
    長堀 紀子, 西村 紳一郎 (担当:共著)
    シーエムシー出版 2004年 p168-178

講演・口頭発表等

  • 「大学活性化に向けた人材育成としての女性研究者支援」  [通常講演]
    長堀 紀子
    平成29年度「大学等における男女共同参画推進セミナー」 2017年11月 口頭発表(招待・特別) 独立行政法人国立女性教育会館 独立行政法人国立女性教育会館
  • 「研究者を研究する?女性研究者支援の立場から」  [通常講演]
    長堀 紀子
    子育て、ライフイベントとフィールドワーク 2017年10月 公開講演,セミナー,チュートリアル,講習,講義等 北海道大学低温科学研究所 北海道大学低温科学研究所
  • 「多様な人材が存分に能力を発揮できる研究環境とは?」  [通常講演]
    長堀 紀子
    北海道大学大学院保健科学研究院保健科学セミナー 2017年09月 口頭発表(一般)
  • 「女子にも男子にも役に立つお話しキャリア開発の枠組みと課題」  [通常講演]
    長堀 紀子
    北海道大学大学理学部高分子学科OGOB談話会 2016年09月
  • "Product Development Utilizing Functional Materials in Hokkaido"  [通常講演]
    長堀 紀子
    Bilateral Symposium on Food Science and Technology between Singapore and Japan 2014年10月 National University of Singapore
  • 「キャリアを考えるってどういうこと?」  [通常講演]
    長堀 紀子
    北海道大学保健科学科・研修会 2006年04月

その他活動・業績

特許

受賞

  • 2006年 日本糖質学会 第10回シアル酸研究会賞
     「糖鎖金ナノ微粒子を基質として用いた糖転移酵素反応の(MA)LDI-TOF MSによる迅速モニタリング」

共同研究・競争的資金等の研究課題

  • 「糖鎖量子ドットを用いた蛍光イメージング法による凝る自体酵素の1分子キネティクス」
    日本学術振興会:科学研究費助成事業 若手研究B
    研究期間 : 2012年 -2013年 
    代表者 : 長堀 紀子
  • 「生細胞相関分光法を用いたゴルジ体酵素の機能的複合体形成のダイナミクス解析」
    内藤記念科学振興財団:内藤記念女性研究者研究助成金
    研究期間 : 2011年 -2013年 
    代表者 : 長堀 紀子
  • 「細胞表層の糖鎖発現プロファイルに基づいた癌特異的プローブの開発」
    国立研究開発法人新エネルギー・産業技術総合開発機構:
    研究期間 : 2008年 -2009年
  • 「マイクロドメイン糖脂質レプリカを用いた細胞特異的認識環状ペプチドの探索」
    日本学術振興会:科学研究費助成事業 若手研究B
    研究期間 : 2007年 -2008年 
    代表者 : 長堀 紀子
  • 「マイクロドメイン糖脂質レプリカナノ微粒子を用いた細胞特異的認識ペプチドの探索」
    秋山記念生命科学振興財団:奨励助成
    研究期間 : 2008年 
    代表者 : 長堀 紀子
  • 「金属ナノ微粒子を用いた選択的レーザー脱離イオン化LDI-MSによる複合糖質の機能探索」
    日本学術振興会:科学研究費助成事業 基盤研究A
    研究期間 : 2005年 -2007年
  • 「糖鎖金属ナノ微粒子を用いた生きた細胞内での酵素反応のリアルタイムモニタリング」
    日本学術振興会:科学研究費助成事業 若手研究B
    研究期間 : 2005年 -2006年 
    代表者 : 長堀 紀子
  • 「細胞内糖鎖機能探索ツールとしての機能性磁性ナノ微粒子の開発」
    公益財団法人 北海道科学技術総合振興センター:若手研究
    研究期間 : 2006年 
    代表者 : 長堀 紀子
  • 「糖鎖金属微粒子を用いた生体内の酵素反応直接モニタリング法の開発」
    公益財団法人 北海道科学技術総合振興センター:若手研究
    研究期間 : 2004年 
    代表者 : 長堀 紀子
  • functional analysis of glycoconjugates

大学運営

委員歴

  • 2020年08月 - 現在   札幌市男女共同参画センター運営協議会   委員
  • 2020年04月 - 現在   科学技術専門家ネットワーク   NISTEP専門調査員


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