Chemical Proteomic Analysis Reveals the Drugability of the Kinome of Trypanosoma brucei

Michael D. Urbaniak, Toby Mathieson, Marcus Bantscheff, Dirk Eberhard, Raffaella Grimaldi, Diego Miranda-Saavedra, Paul Wyatt, Michael A. J. Ferguson, Julie Frearson, Gerard Drewes

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    38 Citations (Scopus)

    Abstract

    The protozoan parasite Trypanosoma brucei is the causative agent of African sleeping sickness, and there is an urgent unmet need for improved treatments. Parasite protein kinases are attractive drug targets, provided that the host and parasite kinomes are sufficiently divergent to allow specific inhibition to be achieved. Current drug discovery efforts are hampered by the fact that comprehensive assay panels for parasite targets have not yet been developed. Here, we employ a kinase-focused chemoproteomics strategy that enables the simultaneous profiling of kinase inhibitor potencies against more than SO endogenously expressed T. brucei kinases in parasite cell extracts. The data reveal that T. brucei kinases are sensitive to typical kinase inhibitors with nanomolar potency and demonstrate the potential for the development of species-specific inhibitors.

    Original languageEnglish
    Pages (from-to)1858-1865
    Number of pages8
    JournalACS Chemical Biology
    Volume7
    Issue number11
    Early online date21 Aug 2012
    DOIs
    Publication statusPublished - 2012

    Keywords

    • INHIBITORS
    • ACCURATE
    • LEISHMANIA
    • QUANTIFICATION
    • IDENTIFICATION
    • DRUG TARGET
    • LIKELIHOOD
    • AFRICAN SLEEPING SICKNESS
    • EUKARYOTIC PROTEIN-KINASES
    • DIFFERENTIATION

    Cite this

    Urbaniak, M. D., Mathieson, T., Bantscheff, M., Eberhard, D., Grimaldi, R., Miranda-Saavedra, D., Wyatt, P., Ferguson, M. A. J., Frearson, J., & Drewes, G. (2012). Chemical Proteomic Analysis Reveals the Drugability of the Kinome of Trypanosoma brucei. ACS Chemical Biology, 7(11), 1858-1865. https://doi.org/10.1021/cb300326z