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Studies on high-dimensional functions of glycoconjugates toward development of new medicines and biomaterials

Research Project

Project/Area Number 10556026
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Bioproduction chemistry/Bioorganic chemistry
Research InstitutionGIFU UNIVERSITY

Principal Investigator

KISO Makoto  Gifu University, Faculty of Agriculture, Professor, 農学部, 教授 (90092931)

Co-Investigator(Kenkyū-buntansha) KAWASE Mitsuo  Nippon Gaishi Co. Ltd., Chief research fellow, 環境装置事業部・バイオ研究課, 課長
KONDO Hirosato  Kanebo Pharmaceutical Co. Ltd., Group reader, 創薬研究所・化学研究部, グループ長
ISHIDA Hideharu  Gifu University, Faculty of Agriculture, Associate Professor, 農学部, 教授 (20203002)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsL-selectin / 6-sulfo sialyl LeィイD1XィエD1 / sialyl LeィイD1XィエD1 / ganglioside / MAG / myelin / セレクチン / GSC-150 / スルファチド / パルボウィルス / グロボシド
Research Abstract

1. Studies on novel, endogenous ligand for selectins, and molecular design for selectin blockers: We have found that GSC-150, a selectin blocker, would be useful for treatment of allergies such as atopic dermatitis, and have developed an efficient procedure for mass production of GSC-150. 6-Sulfo sialyl LeィイD1XィエD1 has been found to be an endogenous ligand for L-selectin on high endothelial venules (HEV) of human lymph nodes (J. Biol. Chem., 273, 11225-11233. 1998), and very recently, a novel 6-sulfo de-N-acetyl sialyl LeィイD1XィエD1 has been discovered to be a superior ligand for L-selectin (Angew. Chem. Int. Ed., 38, 1131-1133, 1999).
2. Studies on α-series (Chol-1) gangliosides, and structure-activity relationship for MAG binding: We have succeeded in an efficient, total synthesis of GT1aα (Glycoconjugate J., in press), and have demonstrated that the internal sialic acid α(1-6)-linked to GalNAc might be replaced by other anionic substituents such as sulfate (Carbohydr. Res., 316, 1-5, 1999; J. Biol. Chem., in press).
Based on these new findings, design and synthesis of novel medicines and biomaterials are now proceeding.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] C.Mitsuoka: "Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes"Proc. Natl. Acad. Sci. USA. 96. 1597-1602 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] X.Zhang: "Chemoenzymatic synthesis of ganglioside GM_4 analogs as potential immunosuppressive agents"J. Carbohydr. Chem.. 18・2. 225-239 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Komba: "The first total synthesis of 60sulfo-de-N-acetylsialyl Le^x ganglioside: a superior ligand for human L-selectin"Angew. Chem. Int. Ed.. 38・8. 1131-1133 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yu-The Li: "Structural basis for the resistance of Tay-Sachs ganglioside GM_2 to enzymatic degradation"J. Biol. Chem.. 274・15. 10014-10018 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] C.Galustian: "L-selectin interaction with novel mono- and multisulfated Le^x sequences in comparison with the potent ligand 3'-sulfated Le^a"J. Biol. Chem.. 274・26. 18213-18217 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Sawada: "Ganglioside GDIα analogues as high-affinity ligands for myelin-associated glycoprotein (MAG)"Carbohydr. Res.. 316. 1-5 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 木曽 真: "生物化学実験法42・生理活性糖鎖研究法"学会出版センター. 239 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Ikami: "Methods in Enzymology"Academic Press. 748 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mitsuoka, C., Ohmori, K., Kimura, N., Kanamori, A., Komba, S., Ishida, H., Kiso, M. and Kannagi, R.: "Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes."Proc. Natl. Acad. Sci. USA. 96. 1597-1602 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Zhang, X., Kamiya, T., Otsubo, N., Ishida H. and Kiso, M.: "Chemoenzymatic synthesis of ganglioside GM4 analogs as potential immunosuppressive agents1."J. Carbohydr. Chem.. 18(2). 225-239 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Komba, S., Galustian, C., Ishida, H., Feizi, T., Kannagi, R. and Kiso, M.: "First total synthesis of 6-sulfo de-N-acetyl-sialyl lewis x ganglioside: a superior ligand for human L-selectin"Angew. Chem. Int. Ed. Engl.. 38. 1131-1133 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Li, Y.-T., Li, S.-C., Hasegawa, A., Ishida, H., Kiso, M., Bernardi, A., Brocca, P., Raimondi, L. and Sonnino, S.: "Structural basis for the resistance of Tay-sachs ganglioside GM2 to enzymatic degradation."J. Biol. Chem.. 274. 10014-10018 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Galustian, C., Lubineau, A., Narvor, C., Kiso, M., Brown, G. and Feizi, T.: "L-selectin interactions with novel mono- and multisulfated lewis x sequences in comparison with the potent ligand 3'-sulfated lewis a."J. Biol. Chem.. 274. 18213-18217 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sawada, N., Ishida H., Collins, B.E., Schnaar, R.L. and Kiso, M.: "Ganglioside GD1α analogues as high-affinity ligands for myelin-associated glycoprotein (MAG)."Carbohydr. Res.. 316. 1-5 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikami, T. et al.: "Synthesis and biological activity of glycolipids, with a focus on gangliosides and sulfatide analogs."Methods in Enzymol.. 311. 547-568 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kiso, M.: "Research Methods in Bioactive Glycoproteins (in Japanese)"Gakkai Publishing Center Co. Ltd.. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] C.Mitsuoka: "Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes"Proc. Natl. Acad. Sci. USA. 96. 1597-1602 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] X. Zhang: "Chemoenzymatic synthesis of ganglioside GM4 analogs as potential immunosuppressive agents"J. Carbohydr. Chem.. 18・2. 225-239 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] S. Komba: "The first total synthesis of 6-sulfo-de-N-acetysialyl Le^X ganglioside; a superior ligand for human L-selectin"Angew. Chem. Int. Ed.. 38・8. 1131-1133 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yu-The Li: "Structural basis for the resistance of Tay-Sachs ganglioside GM2 to enzymatic degradation"J. Biol. Chem.. 274・15. 10014-10018 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] C. Galustion: "L-selectin interactions with novel mono-and multisulfated Le^X sequences in comparison with the potent ligand 3'-sulfated Le^a"J. Biol. Chem.. 274・26. 18213-18217 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Sawada: "Ganglioside GD1α analogues as high affinity ligands for myelin-associated glycoprotein(MAG)"Carbohydr. Res.. 316. 1-5 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 木曽真: "生物化学実験法42・生理活性糖鎖研究法"学会出版センター. 239 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T. Ikami: "Methods in Enzymology"Academic Press. 748 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] C.Mitsuoka: "Identification of a Major Carbohydrate Capping Group of the L-selectin Ligand on High Endothelial Venules in Human Lymph Nodes as 6-Sulfo Sialyl Le^X" J.Biol.Chem.273・18. 11225-11233 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Ikami: "Synthetic Studies on Selectin Ligands/Inhibitors : Synthesis and Biological Evalu-ation of Sulfated and Phosphory lated β-D-Galacto and Lactopyran osicks" Chem.Pharm.Bull.46・5. 797-806 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Ikami: "Synthetic Studies on Selectin Ligands/Inhibitors : Synthesis and Inhibitory activity of 2-O-Fucosyl Sulfatides containing 2-Branched Fatty Alkyl Residues." J.Carbohydr.Chem.17・3. 453-470 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Kiyoi: "A stereoselective α-Fucosylation Reaction Using 1-Hydroxy 2,3,4-tri-O-benzyl-L-Fucose Donor for the Practical Synthesis of Selectin Blocker" Bioorg.Med.Chem.Lett.8. 2845-2848 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Ikami: "Synthetic Studies on Selectin Ligands/Inhibitors : Synthesis and Biological Activity of the Sulfated and Phosphorylated Multivalent D-D-Galactopyranosides" J.Carbohydr.Chem.17・485. 499-518 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.S.Mulligan: "In vitro and In Vivo selectin-blocking activities of sulfated lipids and sulfated sialyl compounds." Int.Immunol.10・5. 569-575 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] P.L.Schnaar: "Sphingolipids as Signaling Modulators in the Nervous System" The New York Academy of Sciences, 435 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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