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1998 Fiscal Year Final Research Report Summary

Biological Activity of novel glycosaminoglycan and interaction with binding proteins.

Research Project

Project/Area Number 09672185
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionChiba University

Principal Investigator

TOIDA Toshihiko  Chiba University Faculty of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (60163945)

Project Period (FY) 1997 – 1998
KeywordsAcharan sulfate / oligosaccharides / acticoagulant activity / interaction / glycosaminoglycan / giant snail / NMR spectroscopy / affinity
Research Abstract

We have very recently found a new glycosaminoglycan from African Giant Snail, Achatina fulica, and have characterized that this new glycosaminoglycan is consisting of homogeneous disaccharide (*4GlcNpAcalpha1*4IdoAp2Salpha) repeating unit. This polysaccharide, named acharan sulfate, has a unique sequence belonging in heparan sulfate family and shows angeogenesis activity.
This study examined the hypothesis that contain oligosaccharide sequences in acharan sulfate have high affinity for consensus peptide sequences in proteins present in the extracellular matrix. A variety of different size of oligosaccharides in the range from disaccharide to tetradecasaccharide of acharan sulfate were prepared by partial enzymatic digestion. These oligosaccharides were used to isolate high affinity proteins, which were examined for composition and sequence. Oligosaccharide-protein interactions were examined for : 1. binding affinity (Kd) ; 2. binding specificity ; 3. Binding thermodynamics ; 4. binding … More orientation ; and 5. binding site structural requirements! Peptides will also be synthesized to contain variations of the consensus sequence and modified oligosaccharides such as N-de-acetylated and re-N-sulfonated acharan sulfate, were synthesized to help establish the structure activity relationship for oligosaccharide-peptide interaction. Native protein will be compared with synthetic peptide to confirm specificity of binding. Vitronectin and recombinant acidic fibroblast growth factor are the proteins to be studied because of the important biological consequences of their binding to acharan sulfate/heparin/heparan sulfate. Ultimately, these studies should lead to custom designed peptides that have increased oligosaccharide binding affinity to enhance or attenuate the activities associated with oligosaccharide-protein interaction. These oligosaccharides and peptides represent the starting point for new drug design focused on peptido-mimetics and sulfated oligosaccharide-mimetics. Such new therapeutic agents might be used to regulate a variety of biological processes including angiogenesis, metastasis, atherogenesis, immune responses, HIV infection, and thrombosis. Less

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 丸山智弘 その他4名: "Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation." Carbohydrate Research. 306. 35-43 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 金永植 その他9名: "Determination of the structure of oligosaccharides prepared from acharan sulfate." Glycobiology. 8. 869-877 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 金永植 その他6名: "Characterization of Bacteroids species from human intestine that degrades glycosaminoglycans." Canadian Journal of Microbiology. 44. 423-429 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Duangdeum その他7名: "Formation of a complex containing ATP, Mg and spermine." Journal of Biological Chemistry. 273. 30939-30944 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 金永植 その他6名: "Chemical sulfonation and anticoagulant activity of acharan sulfate." Thrombosis Research. 92. 273-281 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 今成登志男 その他6名: "Oral absorption and clearance of partially depolymerized fucosyl chondroitin sulfate from sea cucumber." Thrombosis Research. 93. 129-135 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Toyoda: "Rapid and sensitive analysis of disaccharide composition in heparin and heparan sulfate by reversed-phase ion-pair chromatography on a 2-micrometer porous silica gel column." J.Chromatogr.830. 197-201 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Imanari: "Oral absorption and clearance of partially depolymerized fucosyl chondroitin sulfate from sea cucumber." Thromb.Res.93. 129-135 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] SJ.Wu: "Chemical sulfonation and anticoagulant activity of acharan sulfate" Thromb.Res.92. 273-281 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] YS.Kim: "Determination of the structure of oligosaccharides prepared from acharan sulfate" Glycobiology. 8. 869-877 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] AH.Ahn: "Characterization of a Bacteroides species from human intestine that degrades glycosaminoglycans" Can.J.Microbiol.44. 423-429 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Maruyama: "Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation." Carbohydr.Res.306. 35-43 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Mitani: "Alteration of hairless mouse skin exposed to chronic UV irradiation and its prevention by hydrocortisone" Photochem.Photobiol.69. 41-46 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Toida: "Structural analysis of heparan sulfate and heparan sulfate oligosaccharides." Trends in glycosci.glycotechnol.10. 125-136 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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