Document Report Card

Basic Information

ID: ALA1154298

Journal: Bioorg Med Chem Lett

Title: Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases.

Authors: Bryant C, Kerr ID, Debnath M, Ang KK, Ratnam J, Ferreira RS, Jaishankar P, Zhao D, Arkin MR, McKerrow JH, Brinen LS, Renslo AR.

Abstract: We describe here the identification of non-peptidic vinylsulfones that inhibit parasite cysteine proteases in vitro and inhibit the growth of Trypanosoma brucei brucei parasites in culture. A high resolution (1.75 A) co-crystal structure of 8a bound to cruzain reveals how the non-peptidic P2/P3 moiety in such analogs bind the S2 and S3 subsites of the protease, effectively recapitulating important binding interactions present in more traditional peptide-based protease inhibitors and natural substrates.

CiteXplore: 19773167

DOI: 10.1016/j.bmcl.2009.08.098