1997 Fiscal Year Final Research Report Summary
Molecular design of BRMs using synthetic peptide libraries
| Project/Area Number |
08557022
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OHMI Shinobu Univ.Tokyo, Inst.Med.Sci., Associate Professor, 医科学研究所, 助教授 (20160046)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATA Ko Univ.Tokyo, Inst.Med.Sci., Research Accosiate, 医科学研究所, 助手 (80207802)
NARIUCHI Hideo Univ.Tokyo, Inst.Med.Sci., Professor, 医科学研究所, 教授 (10012741)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Antagonist / Peptide / Fas / BRM / Cell death / Apoptosis / receptor / Chemical modification |
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| Research Abstract |
To understand the relation between microbiral infection and host cell response we performed molecular design of biological response modifiers (BRMs). Antagonists for apoptosis mediated by Fas/Fas ligand (FasL) system were searched in peptide librareis synthesized on the basis of the primary structure of human FasL,an apoptosis-inducing molecule that binds to Fas on the surface of a target cell. Peptides derived from extracellular part of FasL were screened for Fas binding, structurally designed and finally modified with a dinitrophenyl (Dnp) or a triphenylmethyl (Trt) group to become strong antagonists. A peptide corresponding to residues 215-226 of human FasL was established as an apoptosis-suppressing drug when it was chemically modified with Dnp or Trt. The FasL-derived peptides antagonized human T jurkat apoptosis induced not only by cytotoxic anti-Fas antibodies but also by natural FasL.The anti-Fas antibodies did not compele with our peptides for cell-surface Fas, suggesting that the peptides did not block receptor binding by FasL but that inhibited transmision of death signal to the cytosol.
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