CREATION OF ARTIFICIAL COMPLEX CARBOHYDRATE PROBES AND MODULATION OF HIGHER BIOLOGICAL FUNCTIONS

2009 Fiscal Year Final Research Report

• Project/Area Number: 17101007
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: Gifu University
• Principal Investigator: KISO Makoto Gifu University, 応用生物科学部, 教授 (90092931)
• Co-Investigator(Kenkyū-buntansha): ISHIDA Hideharu 岐阜大学, 応用生物科学部, 教授 (20203002) ; ANDO Hiromune 岐阜大学, 応用生物科学部, 准教授 (20372518) ; YABE Tomio 岐阜大学, 応用生物科学部, 准教授 (70356260) ; KANNAGI Reiji 愛知県がんセンター, 分子病態学部, 部長(研究職) (80161389) ; YUKI Nobuhiro 獨協医科大学, 神経内科, 助教授 (60285913)
• Project Period (FY): 2005 – 2009
• Keywords: 糖鎖 / ガングリオシド / 複合糖質 / 感染 / 癌 / 免疫 / 脳・神経

Research Abstract

糖鎖の中でも特に多彩な生理機能を発現するシアル酸含有スフィンゴ糖脂質ガングリオシドの実践的大量合成法を開発し、800種に及ぶ人工複合糖質プローブの創出に成功しました。この成果は、インフルエンザや細菌毒素の感染、免疫応答、がん、炎症、自己免疫性神経疾患などの病態の理解に世界的な貢献をしました。現在、薬の開発や細胞生物学への先端的応用研究が進行しています。

Research Products

• [Journal Article] A cyclic glucosyl ceramide acceptor as a versatile building block for complex ganglioside synthesis. (2010)
  • Author(s): Fujikawa, K., Nohara, T., Imamura, A., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Tetrahedron Lett. 51 Pages: 1126-1130
• [Journal Article] Efficient synthesis of three types of sialyl 6-O-sulfo Lewis X: probes for the comprehensive search for the interaction between carbohydrates and other biomoleclues. (2009)
  • Author(s): Yamaguchi, M., Ishida, H., Kiso, M.
  • Journal Title: HETEROCYCLES 77 Pages: 333-349
• [Journal Article] Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray. (2009)
  • Author(s): Childs, R.A., Palma, A.S., Wharton, S., Matrosovich, T., Liu, Y., Chai, W., Campanero-Rhodes, M.A., Zhang, Y., Eickmann, M., Kiso, M., Hay, A., Matrosovich, M., Feizi, T.
  • Journal Title: Nature Biotechnology 27 Pages: 797-799
• [Journal Article] Potent small molecule mouse CD22-inhibitors: Exploring the interaction of the residue at C-2 of sialic acid scaffold. (2009)
  • Author(s): Abdu-Allah., Hajjaj Hassan Mohamed, Watanabe, K., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Tsubata, T., Ishida, H., Kiso, M.
  • Journal Title: Bioorg. Med. Chem. Lett. 19 Pages: 5573-5575
• [Journal Article] Synthesis of biotinylated sialoside to probe CD22-ligand interactions. (2009)
  • Author(s): Abdu-Allah., Hajjaj Hassan Mohamed, Watanabe, K., Hayashizaki, K., Iwayama, Y., Takematsu, H., Kozutsumi, Y., Tsubata, T., Ishida, H., Kiso, M.
  • Journal Title: Tetrahedron Lett. 50 Pages: 4488-4491
• [Journal Article] Synthetic study on a(2-8)-linked oligosialic acid employing 1, 5-lactamization as a key step. (2009)
  • Author(s): Tanaka, H., Ando, H., Ishida, H., Kiso, M., Ishihara, H., Koketsu, M.
  • Journal Title: Tetrahedron Lett. 50 Pages: 4478-4481
• [Journal Article] A first total synthesis of ganglioside HLG-2. (2009)
  • Author(s): Iwayama, Y., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Chem. Euro. J. 15 Pages: 4637-4648
• [Journal Article] Ganglioside GQ1b: Efficient total synthesis and the expansion to synthetic derivatives to elucidate its biological roles. (2009)
  • Author(s): Imamura, A., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: J. Org. Chem. 74 Pages: 3009-3023
• [Journal Article] type a in complex with the cell surface co-receptor GT1b insight into the toxin-neuron interaction. (2008)
  • Author(s): Stenmark, P., Dupuy, J., Imamura, A., Kiso, M., Stevens, R.C.
  • Journal Title: PLoS Pathogens 4 Pages: 1-10
• [Journal Article] Design, synthesis, and structure-affinity relationships of novel series of sialosides as CD22-specific inhibitors. (2008)
  • Author(s): Abdu-Allah, Hajjaj Hassan Mohamed, Tamanaka, T., Yu, J., Lu, Z., Sadagopan, M., Adachi, T., Tsubata, T., Kelm, S., Ishida, H., Kiso, M.
  • Journal Title: J. Med. Chem. 51 Pages: 6665-6681
• [Journal Article] Synthesis of ganglioside GM3 analog carrying phytoceramide by employing intramolecular glycosylation as a key reaction. (2008)
  • Author(s): Fujikawa, K., Imamura, A., Ishida, H., Kiso, M.
  • Journal Title: Carbohydr. Res. 343 Pages: 2729-2734
• [Journal Article] A highly efficient construction of GM1 epitope tetrasaccharide and its conjugation with KLH. (2008)
  • Author(s): Yoshikawa, T., Kato, Y., Yuki, N., Yabe. T., Ishida, H., Kiso, M.
  • Journal Title: Glycoconjugate J. 25 Pages: 545-553
• [Journal Article] Effect of structural modifications of ganglioside GM2 on intra-molecular carbohydrate-to-carbohydrate interaction and enzymatic susceptibility. (2008)
  • Author(s): Li, Y.-T., Li, S.-C., Kiso, M., Ishida, H., Mauri, L., Raimondi, L., Bernardi, A., Sonnino, S.
  • Journal Title: Biochim. Biophys. Acta 1780 Pages: 353-361
• [Journal Article] Design and synthesis of versatile ganglioside probes for carbohydrate microarrays. (2008)
  • Author(s): Imamura, A., Yoshikawa, T., Komori, T., Ando, M., Ando, H., Wakao, M., Suda, Y., Ishida, H. Kiso, M.
  • Journal Title: Glycoconjugate J. 25 Pages: 269-278
• [Journal Article] Current relevance of incomplete synthesis and neo-synthesis for cancer-associated alteration of carbohydrate determinants. (2008)
  • Author(s): Kannagi, R., Yin, J., Miyazaki, K., Izawa, M.
  • Journal Title: Biochim. Biophys. Acta 1780 Pages: 525-531
• [Journal Article] Clinical application of functional glycoproteomics-dissection of glycotopes carried by soluble CD44 variants in sera of patients with cancers. (2008)
  • Author(s): Lim, K-T., Miyazaki, K., Kimura, N., Izawa, M., Kannagi, R.
  • Journal Title: Proteomics 8 Pages: 3263-3273
• [Journal Article] Significance of NF-κB/GATA axis in TNF-α-induced expression of 6-sulfated cell-recognition glycans in human T-lymphocytes. (2008)
  • Author(s): Chen, G.-Y., Sakuma, K., Kannagi, R.
  • Journal Title: J. Biol. Chem. 283 Pages: 34563-34570
• [Journal Article] Synthetic glycan ligand excludes CD22 from antigen receptor-containing lipid rafts. (2007)
  • Author(s): Yu, J., Sawada, T., Adachi, T., Gao, X., Takematsu, H., Kozutsumi, Y., Ishida, H., Kiso, M., Tsubata, T.
  • Journal Title: Biochem. Biophys. Res. Commun 360 Pages: 759-764
• [Journal Article] The principal neuronal gD-type 3-O-sulfotransferases and their products in central and peripheral nervous system tissues. (2007)
  • Author(s): Lawrence, R., Yabe, T., HajMohammadi, S., Rhodes, J., McNeely, M., Liu, J., Lamperti, E.D., Toselli, P.A., Lech, M., Spear, P.G., Rosenberg, R.D., Shworak, N.W.
  • Journal Title: Matrix Biol. 26 Pages: 442-455
• [Journal Article] Human B-lymphocytes expressα2-6 sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/siglec-2. (2007)
  • Author(s): Kimura, N., Ohmori, K., Miyazaki, K., Izawa, M., Matsuzaki, Y., Yasuda, Y., Takematsu, H., Kozutsumi, Y., Moriyama, A., Kannagi, R.
  • Journal Title: J. Biol. Chem. 282 Pages: 32200-32207
• [Journal Article] Siglec-7 undergoes a major conformational change when complexed with the (2, 8)-disialylganglioside GT1b. (2006)
  • Author(s): Attrill, H., Imamura, A., Sharma, R.S., Kiso, M., Crocker, P.R., van Aalten, D.M.F.
  • Journal Title: J. Biol. Chem. 281 Pages: 32774-32783
• [Journal Article] Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. (2006)
  • Author(s): Yamada, S., Suzuki, Y., Suzuki, T., Le, M.Q., Nidom, C.A., Sakai-Tagawa, Y., Muramoto, Y., Ito, M., Kiso, M., Horimoto, T., Sinya, K., Sawada, T., Kiso, M., Usui, T., Murata, T., Lin, Y., Hay, A., Haire, L.F., Stevens, D.J., Russell, R.J., Gamblin, S. Yamada, S., Suzu
  • Journal Title: Nature 444 Pages: 378-382
• [Journal Article] The structure of Siglec-7 in complex with sialosides: leads for rational structure-based inhibitor design. (2006)
  • Author(s): Attrill, H., Takazawa, H., Witt, S., Kelm, S., Isecke, R., Brossmer, R., Ando, T., Ishida, H., Kiso, M. Crocker, P.R., van Aalten, D.M.F.
  • Journal Title: Biochem. J. 397 Pages: 271-278
• [Journal Article] Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis x, a selectin ligand expressed on a subset of skin-homing helper memory T cells. (2006)
  • Author(s): Ohmori, K., Fukui, F., Kiso, M., Imai, T., Yoshie, O., Hasegawa, H., Matsushima, K., Kannagi, R.
  • Journal Title: Blood 107 Pages: 3197-3204
• [Journal Article] Di-tert-butylsilylene(DTBS)-directedα-selective synthesis of 4-methylumbelliferyl T-antigen. (2005)
  • Author(s): Imamura, A., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Organic Lett. 7 Pages: 4415-4418
• [Presentation] Synthetic sialosides: biological recognition at molecular and cellular levels, and applications in medicinal chemistry. Assiut Univ. (2010)
  • Author(s): Kiso, M., Ishida, H., Ando, H.
  • Organizer: 7th International Pharmaceutical Science Conference, Egypt
  • Place of Presentation: Egypt(Oral)
  • Year and Date: 20100317-20100318
• [Presentation] Synthetic Ganglioside Probes: Versatile Tools for Bio-membrane Research. (2010)
  • Author(s): Kiso, M.
  • Organizer: The 13th International Membrane Research Forum, The 6th iCeMS International Symposium, Featuring Nano-Meso Membrane Mechanisms
  • Place of Presentation: Hotel Fujita Kyoto(Oral)
  • Year and Date: 20100127-20100129
• [Presentation] シアロ糖鎖の化学合成;分子・細胞レベルにおける生体認識と医学生物学への応用 (2009)
  • Author(s): 安藤弘宗, 石田秀治, 木曽真
  • Organizer: 、第7回糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 、千里ライフサイエンスセンター(大阪)(Oral)
  • Year and Date: 20091207-20091208
• [Presentation] A novel heparin-associated peptide as a visualizing probe. (2009)
  • Author(s): Yabe, T., Hosoda-Yabe, R., Kanamaru, Y., Kiso, M.
  • Organizer: 2009 Annual Meeting of the Society for Glycobiology
  • Place of Presentation: San Diego, California, USA(poster)
  • Year and Date: 20091112-20091115
• [Presentation] A First Synthesis of Lacto-ganglio Series Ganglioside (2009)
  • Author(s): Nakashima, S., Ando, H., Ishida, H., Kiso, M.
  • Organizer: 15th European Carbohydrate Symposium
  • Place of Presentation: Vienna, Austria(Oral)
  • Year and Date: 20090719-20090724
• [Presentation] Synthetic ganglioside probes: versatile tools for elucidation of carbohydrate functions. (2009)
  • Author(s): Kiso, M.
  • Organizer: Symposium on the MESO CONTROL of the cells, by the cells, for the cells-featuring transportsomes-.
  • Place of Presentation: Hotel Fujita Kyoto(Oral)
  • Year and Date: 20090127-20090128
• [Presentation] An efficient synthesis of a series of gangliosides, GM3, GM2 and GM1, by employing intramolecularglycosylation as a key step. (2008)
  • Author(s): Fujikawa, K., Imamura, A., Ishida, H., Kiso, M.
  • Organizer: XXIV International Carbohydrate Symposium
  • Place of Presentation: Oslo, Norway(Oral)
  • Year and Date: 20080727-20080801
• [Presentation] Occurrence of the Cyclic Sialic Acid in Mammalian Cells and Tissues As Demonstrated by Chemical Methods. (2008)
  • Author(s): Kitajima, K., Iwata, S., Kawakami, N., Sato, C., Ando, H., Ohno, H., Ishida, H., Kiso, M. Tagushi, O., Kannagi, R.
  • Organizer: XXIV International Carbohydrate Symposium
  • Place of Presentation: Oslo, Norway(Oral)
  • Year and Date: 20080727-20080801
• [Presentation] Potential Synthetic Targets in Medicinal Chemistry and Cell Biology. (2008)
  • Author(s): Kiso, M.
  • Organizer: SialoGlyco Conference 2008
  • Place of Presentation: Moscow- St. Petersburg, Russia(Oral)
  • Year and Date: 20080721-20080726
• [Presentation] A synthesis of GM1 epitope-KLH conjugate for elucidation of the pathogenic mechanism of the Guillan- Barre Syndrome. (2007)
  • Author(s): Yoshikawa, T., Yuki, N., Yabe, T., Ishida, H., Kiso, M.
  • Organizer: XIX International Symposium on Glycoconjugates
  • Place of Presentation: Cairns, Australia
  • Year and Date: 20070715-20070720
• [Presentation] Di-tert-butylsilylene (DTBS)-directed alpha-glycosidation of galactose/galactosamine toward the assembly of various glycosides. (2007)
  • Author(s): Kiso, M.
  • Organizer: Gordon Research Conferences Tilton School
  • Place of Presentation: Tilton(Oral)
  • Year and Date: 20070617-20070622
• [Presentation] Comparative Protein Modeling of Human Sialidases : Implications for the Design of Selective NEU3 Inhibitors. (2006)
  • Author(s): Magesh, S., Suzuki, T., Miyagi, T., Ishida, H., Kiso, M.
  • Organizer: XXIII International Carbohydrate Symposium
  • Place of Presentation: Whistler, Canada
  • Year and Date: 20060723-20060728
• [Presentation] Lactamized sialyl 6-O-sulfo paragloboside & Lewis X neoglycolipids: synthesis and antigenic reactivity against G159 monoclonal antibody. (2005)
  • Author(s): Yamaguchi, M., Ishida, H., Kanamori, A., Kannagi, R., Kiso, M.
  • Organizer: XVIII International Symposium on Glycoconjugates
  • Place of Presentation: Florence, Italy
  • Year and Date: 20050904-20050909
• [Book] 複合糖質の化学と最新応用技術(正田晋一郎, 稲津敏行編) (2009)
  • Author(s): 安藤弘宗, 石田秀治, 木曽真
  • Total Pages: 37-43
  • Publisher: シーエムシー出版
• [Book] The Fragment molecular orbital method: Practical applications to large molecular systems(D. Fedorov and K. Kitaura, (eds),) (2009)
  • Author(s): Sawada, T., Hashimoto, T., Tokiwa, H., Suzuki, T., Nakano, H., Ishida, H., Kiso, M. Suzuki, Y.
  • Total Pages: 193-215
  • Publisher: Boca Raton(CRC Press)
• [Book] Glycobiology Research Trends (2009)
  • Author(s): Tomio Yabe
  • Total Pages: 109-126
  • Publisher: Science Publishers
• [Book] 医薬応用に向けた糖鎖合成技術の活用「シアル酸グルコシル化反応の改良と共通構造から展開するガングリオシドの系統合成法の探求」遺伝子医学MOOK11 (2008)
  • Author(s): 木曽真, 安藤弘宗, 石田秀治
  • Total Pages: 95-103
  • Publisher: 株式会社メディカルドゥ
• [Book] Selectiveα-sialylation. (2008)
  • Author(s): Ando, H., Kiso, M.
  • Total Pages: 1313-1359
  • Publisher: Springer-Verlag
• [Remarks]
  • URL: http://www1.gifu-u.ac.jp/~kassei/
• [Patent(Industrial Property Rights)] シアリダーゼ活性阻害剤及び抗インフルエンザ薬 (2009)
  • Inventor(s): 木曽真, 石田秀治, サダゴパンマゲッシュ, 鈴木康夫, 宮城妙子
  • Industrial Property Rights Holder: 岐阜大学、中部大学、宮城県
  • Industrial Property Number: 特願2009-298788
  • Filing Date: 2009-12-28
• [Patent(Industrial Property Rights)] CD22分子に対する高親和性を有しB細胞の増殖を増強する化合物 (2009)
  • Inventor(s): 鍔田武志, 木曽真, 石田秀治, アブドゥ・アラハジャジハッサンモハメッド
  • Industrial Property Rights Holder: 東京医科歯科大学、岐阜大学
  • Industrial Property Number: 特願2009-177776
  • Filing Date: 2009-07-30
• [Patent(Industrial Property Rights)] グリコサミノグリカンの検出法及びそのための分子プローブ (2009)
  • Inventor(s): 矢部富雄
  • Industrial Property Rights Holder: 国立大学法人岐阜大学
  • Industrial Property Number: 特願2009-243995
  • Filing Date: 2009-10-23
• [Patent(Industrial Property Rights)] 合成糖脂質含有リポソーム (2008)
  • Inventor(s): 岐阜大学応用生物科学部木曽真, 石田秀治, 山下泰治
  • Industrial Property Rights Holder: 国立大学法人岐阜大学片山化学工業株式会社
  • Industrial Property Number: 国際公開wo2009/104649
  • Filing Date: 2008-02-22
• [Patent(Industrial Property Rights)] スフィンゴ糖脂質のケミカル合成法 (2007)
  • Inventor(s): 木曽真, 石田秀治, 藤川紘樹
  • Industrial Property Rights Holder: 片山化学工業株式会社
  • Industrial Property Number: 特願2008-557184国際公開wo2008/096880
  • Filing Date: 2007-02-09