Elucidation of functions of animal lectins by employing synthetic ligands

2011 Fiscal Year Final Research Report

• Project/Area Number: 21603007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Gifu University
• Principal Investigator: ISHIDA Hideharu 岐阜大学, 応用生物科学部, 教授 (20203002)
• Co-Investigator(Renkei-kenkyūsha): KAWASAKI Toshisuke 立命館大学, 糖鎖工学研究センター, 教授 (50025706) ; TSUBATA Takeshi 東京医科歯科大学, 大学院・疾患生命科学研究部, 教授 (80197756)
• Project Period (FY): 2009 – 2011
• Keywords: 糖鎖リガンド

Research Abstract

Functions of siglec-2 expressed on B cell and mannan-binding protein(MBP) concerned with innate immunity were studied by employing their synthetic ligands as well as inhibitors. A novel, potent inhibitor of siglec-2 was developed based on the structure-activity relationship of a series of sialosides as siglec-2 ligands, and which was found to be significantly effective to protect mice from the infection with influenza virus.

Research Products

• [Journal Article] Design and synthesis of a multivalent heterobifunctional CD22 ligand as a potential immunomodulator (2011)
  • Author(s): Abdu-Allah, H. H. M., Watanabe, K., Daikoku, S., Kanie, O., Tsubata, T., Ando, H., Ishida, H. and Kiso, M.
  • Journal Title: Synthesis Volume: 18 Pages: 2968-2974
  • 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 (2011)
  • Author(s): Abdu-Allah, H. H. M., Watanabe, K., Completo, G. C., Magesh, S., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Paulson, J. C., Tsubata, T., Ando, H., Ishida, H. and Kiso, M.
  • Journal Title: Bioorg. Med. Chem Volume: 19 Pages: 1966-1971
  • Peer Reviewed
• [Journal Article] Highly fucosylated N-glycan ligands for mannan-binding protein expressed specifically on CD26(DPPVI) isolated from a human colorectal carcinoma cell line (2009)
  • Author(s): Kawasaki, N., Lin, C.-W., Inoue, R., Khoo, K.-H., Kawasaki, N., Ma, B. Y., Oka, S., Ishiguro, M., Sawada, T., Ishida, H., Hashimoto, T. and Kawasaki, T.
  • Journal Title: SW1116. Glycobiology Volume: 19 Pages: 437-450
  • Peer Reviewed
• [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, H. H. M., Watanabe, K., Hayashizaki, K., Takaku, C., Tamanaka, T., Takematsu, H., Kozutsumi, Y., Tsubata, T., Ishida, H. and Kiso, M.
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 19 Pages: 5573-5575
  • Peer Reviewed
• [Journal Article] Synthesis of biotinylated sialoside to probe CD22-ligand interactions (2009)
  • Author(s): Abdu-Allah, H. H. M., Watanabe, K., Hayashizaki, K., Iwayama, Y., Takematsu, H., Kozutsumi, Y., Tsubata, T., Ishida, H. and Kiso, M.
  • Journal Title: Tetrahedron Lett Volume: 50 Pages: 4488-4491
  • Peer Reviewed
• [Presentation] Siglec-2阻害剤の効率的合成法の開発 (2012)
  • Author(s): 菅沼勇輝,岩山祐己,植木章晴,今村彰宏,安藤弘宗,石田秀治,木曽真
  • Organizer: 2012年度大会日本農芸化学会
  • Place of Presentation: 京都
  • Year and Date: 20120322-26
• [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. and Kiso, M.
  • Organizer: 13th International Conference on Biology and Chemistry of Sialic Acids-SialoGlyco 2010
  • Place of Presentation: Potsdam, Germany
  • Year and Date: 20100821-26
• [Presentation] Design, synthesis and biological evaluation of novel sialosides as potent and selective inhibitors for siglecs (2010)
  • Author(s): Ishida, H.
  • Organizer: Freie Universitat Berlin
  • Place of Presentation: Germany
  • Year and Date: 2010-08-27
• [Presentation] CD22 ligands : Design synthesis and applications (2009)
  • Author(s): Abdu-Allah, H. H. M., Tamanaka, T., Takaku, C., Yu, J., Lu, Z., Magesh, S., Adachi, T., Tsubata, T., Ishida, H. and Kiso, M.
  • Organizer: The Fifth iCeMS International Symposium "Biomaterials at the interface of chemistry, physics, and biology"
  • Place of Presentation: Clock Tower Cenntennial Hall, Kyoto University
  • Year and Date: 20090727-28
• [Presentation] Exploring structure-affinity relationships of CD22-inhibitors (2009)
  • Author(s): Abdu-Allah, H. H. M., T. Tamanaka, C. Takaku, Yu, J., Lu, Z., Magesh, S., T. Adachi, Tsubata, T., Ishida, H., and Kiso, M.
  • Organizer: CREST国際シンポジウム
  • Place of Presentation: 木更津市(千葉)
  • Year and Date: 20090323-24
• [Presentation] Design and Synthesis of Novel Sialosides as CD-22 Inhibitors (2009)
  • Author(s): Ishida, H.
  • Organizer: Toward Systems Glycobiology 3-Let's talk about sialic acids in Nagoya!-
  • Place of Presentation: 生物機能開発利用研究センター(名古屋)
  • Year and Date: 2009-10-20
• [Remarks]
  • URL: http://www1.gifu-u.ac.jp/~kassei1/
• [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
  • Filing Date: 2009-07-30