Elucidation of functions of animal lectins by employing synthetic ligands

• 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
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 糖鎖リガンド / MBP / シグレック / 動物レクチン / シアル酸 / ルイスa

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] Identification of rare 6-deoxy-D-altrose from an edible mushroom (Lactarius lividatus) (2012)
  • Author(s): Tako, M., Dobashi, Y., Tamaki, T., Konishi, T., Yamada, M., Ishida, H., Kiso, M.
  • Journal Title: Carbohydr.Res. Volume: 350 Pages: 25-30
  • DOI: 10.1016/j.carres.2011.12.016
  • Peer Reviewed
• [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] Synthesis of the Disialic Acid-Embedded Glycan Part of Ganglioside HPG-1 (2011)
  • Author(s): Shimizu, H., Iwayama, Y., Imamura, A., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 75 Issue: 10 Pages: 2079-2082
  • DOI: 10.1271/bbb.110619
  • NAID: 10029873464
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] Design and synthesis of a multivalent heterobifunctional CD22 ligand as apotential immunomodulator (2011)
  • Author(s): Abdu-Allah, H.H.M., Watanabe, K., Daikoku, S., Kanie, O., Tsubata, T., Ando, H., Ishida, H., Kiso, M.
  • Journal Title: Synthesis Volume: 18 Issue: 18 Pages: 2968-2974
  • DOI: 10.1055/s-0030-1260151
  • Peer Reviewed
• [Journal Article] High-affinity ligands of siglec receptors and their therapeutic potentials (2011)
  • Author(s): Sadagopan, M., Ando, H., Tsubata, T., Ishida, H., Kiso, M.
  • Journal Title: Current Medicinal Chemistry Volume: 18 Pages: 3537-3550
  • Peer Reviewed
• [Journal Article] Synthesis of the glycan moiety of ganglioside HPG-7 with an unusualtrimer of sialic acid as the inner sugar residue (2011)
  • Author(s): Iwayama, Y., Ando, H., Tanaka, H., Ishida, H., Kiso, M.
  • Journal Title: Chem.Comm. Volume: 47 Issue: 34 Pages: 9726-9728
  • DOI: 10.1039/c1cc13200h
  • Peer Reviewed
• [Journal Article] Evaluation of a set of C9 N-acyl Neu5Ac2en mimetics as viral sialidase selective inhibitors (2011)
  • Author(s): S. Magesh, N. Sriwilaijaroen, M. Setsuko, H. Ando, M. Taeko, Y. Suzuki, H. Ishida and M. Kiso
  • Journal Title: International J. Medicinal Chemistry Volume: Vol.2011 Pages: 7-7
  • DOI: 10.1155/2011/539245
  • Peer Reviewed
• [Journal Article] Synthesis of 6-deoxy-D-altrose used as an authentic sample to identify anunknown monosaccharide isolated from the fruiting body of an edible mushroom (2011)
  • Author(s): Yamada, M., Yoshida, F., Ando, H., Ishida, H., Kiso, M., Tako, M.
  • Journal Title: HETEROCYCLES Volume: 82 Pages: 1699-1704
  • Peer Reviewed
• [Journal Article] The first total synthesis of ganglioside Ga1NAc-GD1a, a target molecule for autoantibodies in Guillain-Barre syndrome (2011)
  • Author(s): Fujikawa, K., Nakashima, S., Konishi, M., Fuse, T., Komura, N., Ando, T., Ando, H., Yuki, N., Ishida, H., Kiso, M.
  • Journal Title: Chem.Eur.J. Volume: 17 Issue: 20 Pages: 5461-5651
  • DOI: 10.1002/chem.201003357
  • Peer Reviewed
• [Journal Article] The total synthesis of the neurogenic ganglioside LLG-3 isolated from the starfish Linckia laevigata (2011)
  • Author(s): Tamai, H., Ando, H., Tanaka, H., Hosoda-Yabe, R., Yabe, T., Ishida, H., Kiso, M.
  • Journal Title: Angew.Chem.Int.Ed.Engl. Volume: 50 Issue: 10 Pages: 2330-2333
  • DOI: 10.1002/anie.201006035
  • 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., 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 Issue: 6 Pages: 1966-1971
  • DOI: 10.1016/j.bmc.2011.01.060
  • Peer Reviewed
• [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 Issue: 2 Pages: 588-597
  • DOI: 10.1002/chem.201002184
  • 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., 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] Highly fucosylated N-glycan ligands for mannan-binding protein expressed specifically on CD26 (DPPVI) isolated from a human colorectal carcinoma cell line, SW1116 (2010)
  • 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., Kawasaki, T.
  • Journal Title: Glycobiology 19 Pages: 437-450
  • 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
• [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
  • Peer Reviewed
• [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., Tshbata, T., Ishida, H., Kiso, M.:
  • Journal Title: Tetrahedron Lett. 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
• [Presentation] 蛍光ガングリオジドプローブの合成と1分子追跡実験によるラフト分配特性の解析 (2011)
  • Author(s): 河村奈緒子, 安藤弘宗, 池田泰祐, 鈴木健一, 石田秀治, 楠見明弘, 木曽真
  • Organizer: 第9回糖鎖科学名古屋拠点「若手の力」フォーラム
  • Place of Presentation: 岐阜
  • Year and Date: 2011-10-22
• [Presentation] トラフナマコ由来生理活性ガングリオシドHPG-7の全合成 (2011)
  • Author(s): 岩山祐己, 安藤弘宗, 石田秀治, 木曽真
  • Organizer: 第9回糖鎖科学名古屋拠点「若手の力」フォーラム
  • Place of Presentation: 岐阜
  • Year and Date: 2011-10-22
• [Presentation] 新規環状グルコシルセラミド受容体を用いたガングリオシドGa1NAc-GM1bの全合成 (2011)
  • Author(s): 小西美紅, 藤川紘樹, 中島慎也, 河村奈緒子, 安藤弘宗, 石田秀治, 木曽真
  • Organizer: 第9回糖鎖科学名古屋拠点「若手の力」フォーラム
  • Place of Presentation: 岐阜
  • Year and Date: 2011-10-22
• [Presentation] ALS様疾患に関連するハイブリッド型ガングリオシドの効率的全合成研究 (2011)
  • Author(s): 中島慎也, 安藤弘宗, 今村彰宏, 石田秀治, 結城伸泰, 木曽真
  • Organizer: 第9回糖鎖科学名古屋拠点「若手の力」フォーラム
  • Place of Presentation: 岐阜
  • Year and Date: 2011-10-22
• [Presentation] シアル酸セレノグリコシドの合成研究 (2011)
  • Author(s): 林知衣香, 毛受雅典, 安藤隆幸, 鈴木康夫, 安藤弘宗, 石田秀治, 木曽真
  • Organizer: 第9回糖鎖科学名古屋拠点「若手の力」フォーラム
  • Place of Presentation: 岐阜
  • Year and Date: 2011-10-22
• [Presentation] Development of ganglioside probes as raft markers (2011)
  • Author(s): Ando, H., Komura, N., Chadda, R., Tsuboi, H., Ikeda, T., Tanaka, K., Suzuki, K., Kusumi, A., Ishida, H., Kiso, M.
  • Organizer: 第71回岡崎コンファレンス～糖鎖分子科学の新たな展望～
  • Place of Presentation: 愛知
• [Presentation] Development of fluorescent ganglioside probes for characterizing raft meso-domains in the plasma membrane using single-molecule tracking (2011)
  • Author(s): Ando, H., Suzuki, K.G.N., Komura, N., Chadda, R., Tsuboi, H., Ikeda, T., Tanaka, K., Ishida, H., Kusumi, A., Kiso, M.
  • Organizer: 3rd iCeMS Retreat
  • Place of Presentation: 奈良
• [Presentation] Synthesis and enzymatic study of novel selenoglycoside (2011)
  • Author(s): Ando, T., Ando, H., Kawai, Y.,Tamai, R.,Ishida, H., Kiso, M.
  • Organizer: 16th European Carbohydrate Symposium
  • Place of Presentation: イタリア
• [Presentation] 脂質ラフトの1分子追跡実験を指向した蛍光ガングリオシドプローブの合成と機能検証2 (2011)
  • Author(s): 河村奈緒子, 安藤弘宗, 池田泰祐, 鈴木健一, 楠見明弘, 石田秀治, 木曽真
  • Organizer: 日本ケミカルバイオロジー学会第6回年会
  • Place of Presentation: 東京
• [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] 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
• [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-Sialo Glyco 2010
  • Place of Presentation: ポツダム(ドイツ)
• [Presentation] Synthetic sialosides : biological recognition at molecular and cellular levels, and applications in medicinal chemistry (2010)
  • Author(s): Kiso, M., Ishida, H., Ando, H.
  • Organizer: Assiut Univ. 7th International Pharmaceutical Science Conference
  • Place of Presentation: アシュート(エジプト)
• [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
• [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
• [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)
• [Presentation] CD22 ligands : Design synthesis and applications (2009)
  • Author(s): Abdu-Allah, H.H.M., Tamanaka, T., Takaku, C., Yu, J., Lu, Z., Sadagopan, M., Adachi, T., Tsubata, T., Ishida, H., Kiso, M.
  • Organizer: The Fifth iCeMS International Symposium "Biomaterials at the interface of chemistry, physics, and biology"
  • Place of Presentation: 京都大学(京都)
• [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://www1.gifu-u.ac.jp/~kassei1/
• [Remarks]
  • URL: http://www1.gifu-u.ac.jp/~kassei/
• [Remarks]
  • URL: http://wwwl.gifu-u.ac.jp/~kassei/
• [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
• [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: 2009-177776
  • Filing Date: 2009-07-30