シアロ糖鎖を足場とする新機能分子の創製と革新的利用技術の創出

2010 Fiscal Year Annual Research Report

• Project/Area Number: 22380067
• Research Category: Grant-in-Aid for Scientific Research (B)
• Research Institution: Gifu University
• Principal Investigator: 木曽 真 岐阜大学, 応用生物科学部, 教授 (90092931)
• Co-Investigator(Kenkyū-buntansha): 石田 秀治 岐阜大学, 応用生物科学部, 教授 (20203002)
• Keywords: ガングリオシド / シアロ糖鎖 / 自己免疫性神経疾患 / CD22 / インフルエンザ / シアリダーゼ阻害剤

Research Abstract

(1) 新戦略に基づくガングリオシド合成法の革新と応用:分子内グリコシル化を鍵反応とする大環状グルコシルセラミドアクセプターの開発を行い、a-系列ガングリオシドGM3,GM2,GM1の系統的カセット合成に成功した(Tetrahedron Lett.,51,1126-1130,2010)。これらの人工ガングリオシドは、標的指向性グライコリポソーム(グライコリポ)の構成成分として実用化された。
(2) 自己免疫性神経疾患に関係する新奇ガングリオシドの全合成と高度利用:上記の新規ガングリオシド合成法を応用して、自己免疫性神経疾患に関係するGalNAc-GDla及びALS様神経疾患に関係するハイブリッド型ガングリオシドの全合成に世界で初めて成功した(Chem.Eul.J.,17,588-597,2011)。
(3) CD22(Siglec-2)高親和性リガンドの開発:ビオチン化シアロ糖鎖プローブ(GSC-660)を用いたin vitroスクリーニングによって、MAG(Siglec-4a)と選択性を有する新たなCD22高親和性リガンドの開発に成功した(Bioorg.Med.Chem.,19,1966-1971,2011)。
(4) シアロ糖鎖を足場とするウィルス感染機構の解明と新規シアリダーゼ阻害剤の創製:新型パンデミックA(H_1N_1)インフルエンザウィルスのシアロ糖鎖結合特異性、ならびに、H3N8型ウィルスの感染及び病原性について解析し(J.Virol.,84,12069-12074,2010;Influenza and Other Respiratory Viruses,4,345-351,2010)、新規シアリダーゼ阻害剤の開発を行った(Anti-Infective Agents in Medicinal Chemistry,9,198-204,2010)。

Research Products

• [Journal Article] A first total synthesis of a hybrid-type ganglioside associated with amyotrophic lateral sclerosis like disorder (2011)
  • Author(s): Nakashima, S., Ando, H., Imamura, A., Yuki, N., Ishida, H., Kiso, M.
  • Journal Title: Chem. Eur. J. Volume: 17 Pages: 588-597
  • Peer Reviewed
• [Journal Article] CD22-Antagonists with nanomolar potency : The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold (2010)
  • Author(s): Abdu-Allah, H.H.M., Watanabe, K., Completo, G.C., Sadagopan, M., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Paulson, J.C., Tsubata, T., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Bioorg. Med. Chem. Volume: 19 Pages: 1966-1971
  • Peer Reviewed
• [Journal Article] Investigation of 2-fluoro benzoic acid derivatives as influenza A viral sialidase selective inhibitors (2010)
  • Author(s): Sadagopan, M., Sriwilaijaroen, N., Vats, S., Ando, H., Miyagi, T., T., S., Ishida, H., Kiso, M.
  • Journal Title: Anti-Infective Agents in Medicinal Chemistry Volume: 9 Pages: 198-204
  • Peer Reviewed
• [Journal Article] Use of structure-based virtual screening in the investigation of novel human sialidase inhibitors. (2010)
  • Author(s): Sadagopan, Magesh, Moriya, S., Suzuki, T., Miyagi, T., Ishida, H., Kiso, M.
  • Journal Title: Med. Chem. Res. Volume: 19 Pages: 1273-1286
  • Peer Reviewed
• [Journal Article] Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus (2010)
  • Author(s): Liu, Y, Childs, R.A., Matrosovich, T., Wharton, S., Palma, A.S., Chai, W, Daniels, R., Gregory, V., Uhlendorff, J., Kiso, M., Klenk, H.-D., Hay, A., Feizi, T., Matrosovich, M.
  • Journal Title: J. Virol. Volume: 84 Pages: 12069-12074
  • Peer Reviewed
• [Journal Article] Members of a novel protein family containing microneme adhesive repeat domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites (2010)
  • Author(s): Friedrich, N., Santos, J.M., Liu, Y., Palma, A.S., Leon, E., Saouros, S., Kiso, M., Blackman, M.J., Matthews, P., Feizi, T., Soldati-Favre, D.
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 2064-2076
  • Peer Reviewed
• [Journal Article] Infectivity and pathogenicity of canine H3N8 influenza A virus in horses. (2010)
  • Author(s): Yamanaka, T., Tsujimura, K., Kondo, T., Matsumura, T., Ishida, H., Kiso, M., Hidari, K.I.P.J., Suzuki, T.
  • Journal Title: Influenza and Other Respiratory Viruses Volume: 4 Pages: 345-351
  • Peer Reviewed
• [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. Volume: 51 Pages: 1126-1130
  • Peer Reviewed
• [Presentation] Design, synthesis and biological evaluation of novel sialosides as potent and selective inhibitors for siglecs (2010)
  • Author(s): Abdu-Allah, H.H.M., Ishida, H., Watanabe, K., Tsubata, T., Completo, G., Paulson, J. C., Ando, H., Kiso, M.
  • Organizer: 13th International Conference on Biology and Chemistry of Sialic Acids-SialoGlyco 2010
  • Place of Presentation: ポツダム(ドイツ)
  • Year and Date: 20100821-20100826
• [Presentation] Novel gangliosides synthesis toward applications in medicinal chemistry and cell biology (2010)
  • Author(s): Kiso, M., Ishida, H., Ando, H.
  • Organizer: 13th International Conference on Biology and Chemistry of Sialic Acids - SialoGlyco 2010
  • Place of Presentation: ポツダム(ドイツ)
  • Year and Date: 20100821-20100826
• [Presentation] A first total synthesis of ganglioside GalNAc-GD1a by employing intramolecular glycosylation as a key step (2010)
  • Author(s): Fujikawa, K., Konishi, M., Imamura, A., Ando, H., Ishida, H., Kiso, M.
  • Organizer: 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 20100801-20100806
• [Presentation] Examination of the Glc-Cer-based approaches toward systematic ganglioside synthesis (2010)
  • Author(s): Nakashima, S., Fujikawa, K., Komura, N., Saito, R., Konishi, M., Ando, H., Ishida, H., Kiso, M.
  • Organizer: 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 20100801-20100806
• [Presentation] Synthetic Study on Novel Bioactive Ganglioside HPG-7 from H. pervicax (2010)
  • Author(s): Iwayama, Y., Ando, H., Ishida, H., Kiso, M.
  • Organizer: 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 20100801-20100806
• [Presentation] A First Total Synthesis of Ganglioside LLG-3 from Echinoderms (2010)
  • Author(s): Tamai, H., Ando, H., Ishida, H., Kiso, M.
  • Organizer: 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 20100801-20100806
• [Presentation] Synthesis and functional evaluation of fluorescent GM3 probes (2010)
  • Author(s): Komura, N., Ando, H., Tanaka, K., Suzuki, K., Kusumi, A., Ishida, H., Kiso, M.
  • Organizer: 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 20100801-20100806
• [Presentation] Structure of sialyloligosaccharide recognized by Mycoplasma leg proteins (2010)
  • Author(s): Kasai, T., Nakane, D., Ishida, H., Ando, H., Kiso, M., Miyata, M.
  • Organizer: 18th International Congress of the International Organization for Mycoplasmology
  • Place of Presentation: キャンチャーノテルメ(イタリア)
  • Year and Date: 20100711-20100716
• [Presentation] Mycoplasma mobileとMycoplasmapneumoniaeの"あし"が認識するシアル酸オリゴ糖の構造 (2010)
  • Author(s): 笠井大司, 中根大介, 石田秀治, 安藤弘宗, 木曽真, 宮田真人
  • Organizer: 第37回日本マイコプラズマ学会学術集会
  • Place of Presentation: 国立感染症研究所(東京)
  • Year and Date: 20100610-20100611
• [Presentation] 糖鎖を用いた感染と免疫の制御 (2010)
  • Author(s): 石田秀治
  • Organizer: 岐阜健康長寿・創薬推進機構第2回異分野交流研究会「岐阜発、人類の健康保持と創薬への挑戦
  • Place of Presentation: 岐阜薬科大学大学院講義室
  • Year and Date: 2010-12-10
• [Presentation] 糖鎖の機能を利用する:薬物送達への応用 (2010)
  • Author(s): 石田秀治
  • Organizer: アグロサイエンスカフェ～あんな研究、こんな技術～
  • Place of Presentation: 愛知県産業労働センターウィンクあいち
  • Year and Date: 2010-12-07
• [Presentation] Design, synthesis and biological evaluation of novel sialosides as potent and selective inhibitors for siglecs (2010)
  • Author(s): Ishida, Hideharu
  • Organizer: Lecture
  • Place of Presentation: ベルリン(ドイツ)
  • Year and Date: 2010-08-27
• [Book] Methods In Enzymology, Glycomics (2010)
  • Author(s): Ando, H., Ishida, H., Kiso, M.
  • Total Pages: 664
  • Publisher: Elsevier
• [Book] コールドスプリングハーバー糖鎖生物学第2版 (2010)
  • Author(s): 秋元義弘, 安形高志, 安藤弘宗, 池北雅彦, 石田秀治, 岡島徹也, 掛樋一晃, 神奈木玲児, 木曽真, 北島健, 木下タロウ, 木全弘治, 久野淳, 佐藤ちひろ, 鈴木康夫, 竹川薫, 館野浩章, 谷口直之, 永井尚子, 羽渕脩躬, 浜村和紀, 平林淳, 古川圭子, 古川鋼一, 堀戸重臣, 宮坂昌之, 矢部富雄, 山内祥生
  • Total Pages: 651
  • Publisher: 丸善
• [Remarks]
  • URL: http://wwwl.gifu-u.ac.jp/~kassei/