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1998 Fiscal Year Final Research Report Summary

Analyses and application of the recognition mechanism of carbohydrate structure by carbohydrate-binding antibiotics.

Research Project

Project/Area Number 09680600
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Structural biochemistry
Research InstitutionTokai University, School of Engineering

Principal Investigator

MIZUOCHI Tsuguo  Tokai University, School of Engineering, Professor, 工学部, 教授 (90133149)

Co-Investigator(Kenkyū-buntansha) NAKATA Munehiro  Tokai University, School of Engineering, Associate Professor, 工学部, 助教授 (00266371)
Project Period (FY) 1997 – 1998
Keywordscarbohydrate-binding antibiotics / neoglycolipid / antifungal agent / oligosaccharide probe / HIV
Research Abstract

Pradimicin A and its derivative BMY-28864 with anti-HIV and anti-fungal activities have been shown to be carbohydrate-binding antibiotics belonging to a novel category by our recent studies. In this study, for 17 Pradimicin A derivatives whose structures had been clarified but whose carbohydrate-binding activity and anti-HIV activity were unknown, the ability, specificity, and affinity of their binding to oil-gosaccharide chains were investigated using HIV glycoprotein gpl2O, various natural and artificial glycoproteins, and artificial glycohipids not only to develop a more effective anti-HIV carbohydrate-binding agent using the derivatives as lead compounds, but also to obtain drug design information for new agents against other bacterial and viral infections. The results showed that four of the 17 Pradimicin A derivatives examined exhibited a carbohydrate-binding activity as in the case of Pradimicin A and BMY-28864, and that three of them showed a stronger binding affinity than Pradimicin A and BMY-28864. These findings suggest that these substances are of carbohydrate-binding and very promising also as an anti-HIV agent. Interestingly, one of the four derivatives with carbohydrate-binding nature did not have any anti- fungal effect. Therefore, more accurate information about intramolecular sites required for the drug design could be obtained through detailed investigations on the relationship between the structure, carbohydrate-binding activity, and physiologicaleffects of these substances and on recognition sites in oligosaccharide chains. In addition, a stable conformation of Pradimicin A under vacuum condition could be figured by calculation. The findingss in this study are therefore considered to serve as an important drug design information for the development of more potent and effective anti-HIV agents with carbohydrate-binding property in the future.

  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Moriwaki, T.: "Alteration of N-linked oligosaccharide structures of human chorionic gonadotropin β-subunit by disruption of disulfide bonds" Glycoconjugate J.14. 225-229 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中田宗宏: "糖鎖異常IgGとマンノース結合蛋白質による補体系の活性化" 臨床免疫. 29. 568-572 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中田宗宏: "慢性関節リウマチにおけるIgG糖鎖異常の意義" 医学のあゆみ. 182. 568-572 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakata, M.: "Effect of aromatic nitroso-compounds on superoxide-generating activity in newtisphils." J.Biochem.122. 188-192 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nasuda, A.-K.: "Mechanisms of nitroso compound induced inhibition of superoxide generation in neutrophils." J.Biochem.122. 550-555 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shikata, K.: "Structural changes in the oligosaccharide moiety of human IgG with aging" Glycoconjugate J.15. 683-689 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tang, W.: "Detection of disease-specific augmentation of abnormal in munoglobulin G in sera of patients with rheumatsid arthritis." Glycoconjugate J.15. 929-934 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tang, W.: "Binding specificities of lectirs to immobilized glycoproteins and oligosaccharides." Acta Medica Okayama. 52. 311-318 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukasawa, M.: "Liposome oligomannose-coated with neoglycolipid, a new candidate for a safe adjuvant for induction of CD8^+ cytotoxicT lymphocyte" FEBS Lett.441. 353-356 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuochi, T.: "Oligomannose-coated liposome with neoglycolipid : a strategy of AIDS vaccine with emphasis on cell-mediated innurity" Biochim.Biophys.Acta. (印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuochi, T.: "The role of oligosaccharide chains in HIV infection" J. Infect.Chemother.(印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中田宗宏: "HIVと糖鎖" 蛋白質・核酸・酵素. 43. 2567-2573 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 唐偉: "抗ガン剤の作用機序と感受性" 癌治療と宿主. 10. 377-387 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山本一彦: "早期リウマチの診断と治療の実態" The Medical & Test Journal. 668. 4-9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Moriwaki T.: "Alteration of N-linked oligosaccharide structures of human chorionic gonadotropin beta-subunit by disruption of disulfide bonds." Glycoconjugate J.14. 225-229 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakata, M.: "Effect of aromatic nitroso-compounds on superoxide-generat-ing activity in neutrophils." J.Biochem.122. 188-192 (1977)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nasuda-Kouyama, A.: "Mecanisms of nitroso compound-induced inhibition of superox-ide generation in neutrophils : fluorescence quenching of perylene by ntroso-compounds in the membrane fractions of neutrophils." J.Biochem.122. 550-555 (1977)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakata, M.: "Abnormality in IgG oligosaccharides and activation of comple-ment system by mannose-binding protein." Clinical Immunology. 29. 162-168 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakata, M.: "Significance of abnormal glycosylation of immunoglobulin G in rheumatoid arthritis." Journal of Clinical and Experimental Medicine. 182. 568-572 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shikata, K.: "Structural changes in the oligosaccharide moiety of human IgG with aging." Glycoconjugate J.15. 683-689 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tang., W.: "Detection of disease-specific augmentation of abnormal immu-noglobulin G in sera of patients with rheumatoid arthritis." Glycoconjugate J.15. 929-934 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tang., W.: "Binding specificities of lectins to immobilized glycoproteins and oligosaccharides differ from those of immobilized lectins to oligosaccharides." Acta Medica Okayama. 52. 311-318 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukasawa, M.: "Liposome oligomannose-coated with neoglycolipid, a new can-didate for a safe adjuvant for induction of CD8+ cytotoxic T lymphocytes." FEBS Lett.441. 353-356 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakata, M.: "HIV and glycosylation." Protein, Nucleic Acid and Enzyme.43. 2567-2573 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tang., W.: "Mode of action of anti-cancer agents and its sensitivity." Cancer Therapy & Host. 10. 377-387 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizuochi, T.: "Oligomannose-coated liposome with neoglycolipid : a strategy of aids vaccine with emphasis on cell-mediated immunity." Biochim. Biophys. Acta. (submitted). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizouchi, T.: "The role of oligosaccharide chains in HIV infection." J.Infect. Chemother.(submiffed). (1999)

    • 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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