Chemical Proteomic Analysis
Reveals the Drugability
of the Kinome of <i>Trypanosoma brucei</i>
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Abstract
The protozoan parasite <i>Trypanosoma brucei</i> 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 50 endogenously expressed <i>T. brucei</i> kinases
in parasite cell extracts. The data reveal that <i>T. brucei</i> kinases are sensitive to typical kinase inhibitors with nanomolar
potency and demonstrate the potential for the development of species-specific
inhibitors