Cancer Institute A national cancer institute
designated cancer center

Matthew Bogyo

Publication Details

  • Novel aza peptide inhibitors and active-site probes of papain-family cysteine proteases CHEMBIOCHEM Verhelst, S. H., Witte, M. D., Arastu-Kapur, S., Fonovic, M., Bogyo, M. 2006; 7 (6): 943-950


    Recent characterization of multiple classes of functionalized azapeptides as effective covalent inhibitors of cysteine proteases prompted us to investigate O-acyl hydroxamates and their azapeptide analogues for use as activity-based probes (ABPs). We report here a new class of azaglycine-containing O-acylhydroxamates that form stable covalent adducts with target proteases. This allows them to be used as ABPs for papain family cysteine proteases. A second class of related analogues containing a novel O-acyl hydroxyurea warhead was found to function as covalent inhibitors of papain-like proteases. These inhibitors can be easily synthesized on solid support, which allows rapid optimization of compounds with improved selectivity and potency for a given target enzyme. We present here one such optimized inhibitor that showed selective inhibition of falcipain 1, a protease of the malaria-causing parasite, Plasmodium falciparum.

    View details for DOI 10.1002/cbic.200600001

    View details for Web of Science ID 000238171400014

    View details for PubMedID 16607671

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