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ID: ALA1130869

Journal: Bioorg Med Chem Lett

Title: Peptide-based inhibitors of the hepatitis C virus serine protease.

Authors: Llinàs-Brunet M, Bailey M, Fazal G, Goulet S, Halmos T, Laplante S, Maurice R, Poirier M, Poupart MA, Thibeault D, Wernic D, Lamarre D.

Abstract: Hexapeptide DDIVPC-OH is a competitive inhibitor of the hepatitis C virus (HCV) NS3 protease complexed with NS4A cofactor peptide. This hexapeptide corresponds to the N-terminal cleavage product of an HCV dodecapeptide substrate derived from the NS5A/5B cleavage site. Structure-activity studies on Ac-DDIVPC-OH revealed that side chains of the P4, P3 and P1 residues contribute the most to binding and that the introduction of a D-amino acid at the P5 position improves potency considerably. Furthermore, there is a strong preference for cysteine at the P1 position and conservative replacements, such as serine, are not well tolerated.

CiteXplore: 9873421

DOI: 10.1016/s0960-894x(98)00299-6