2. Academic Validation
  3. Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases

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

  • Bioorg Med Chem Lett. 2009 Nov 1;19(21):6218-21. doi: 10.1016/j.bmcl.2009.08.098.
Clifford Bryant 1,  Iain D Kerr,  Moumita Debnath,  Kenny K H Ang,  Joseline Ratnam,  Rafaela S Ferreira,  Priyadarshini Jaishankar,  DongMei Zhao,  Michelle R Arkin,  James H McKerrow,  Linda S Brinen,  Adam R Renslo
Affiliations

Affiliation

  • 1 Small Molecule Discovery Center, University of California, San Francisco, CA 94158, USA.
PMID: 19773167 DOI: 10.1016/j.bmcl.2009.08.098
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.

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