Inhibition of hepatitis C virus NS3 protease by peptides derived from complementarity-determining regions (CDRs) of the monoclonal antibody 8D4: Tolerance of a CDR peptide to conformational changes of a target

Kouhei Tsumoto, Satoru Misawa, Yoichi Ohba, Takamasa Ueno, Hideya Hayashi, Nobuhiro Kasai, Hideki Watanabe, Ryutaro Asano, Izumi Kumagai

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

We have synthesized and characterized peptides derived from complementarity-determining regions (CDRs) of 8D4, a mouse monoclonal antibody against NS3 protease domain of hepatitis C virus. 8D4 inhibits enzymatic activity without its cofactor, NS4A peptide. One of the synthetic peptides derived from CDRs, CDR1 of the heavy-chain (CDR-H1) peptide strongly inhibited NS3 protease activity competitively in the absence of NS4A and non-competitively in the presence of NS4A. Moreover, cyclic CDR-H1 peptides bridged by disulfide inhibited NS3 protease more potently. The chain length of the CDR-H1 peptide is critical for strong inhibition, even when the peptide is circularized. This finding suggests the importance of peptide conformation. In contrast to a cognate antibody molecule, CDR-derived peptides may provide good ligands for target molecules by having a tolerance to conformational changes of the targets caused by cofactor binding or mutation.

Original languageEnglish
Pages (from-to)77-82
Number of pages6
JournalFEBS Letters
Volume525
Issue number1-3
DOIs
Publication statusPublished - 2002 Aug 14

Keywords

  • Antibody
  • CDR peptide
  • Circularization
  • Conformational change
  • NS3 protease

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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