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.
