Identification of Hypothemycin Targets in T. brucei

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Investigator: Jack W. Taunton, PhD
Sponsor: Kosan Biosciences, Inc.

Location(s): United States

Description

Hypothemycin is a natural product known to irreversibly inhibit a subset of kinases that contain a non-conserved cysteine in their active site. Although its in vitro selectivity profile is known,what it targets in a more "realistic", in vivo context remains mostly unknown. We have recently synthesized an analog of hypothemycin that mirrors the activity of its parent and allows us to use Click Chemistry to identify those targets that it covalently labels. In collaboration with the UCSF Mass Spectrometry Facility, we have used this molecule to identify several essential kinases in Trypanosoma brucei, the causative agent of African sleeping sickness, of which only one was known and studied before.