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Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

ABSTRACT: SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using a chemo-proteomic approach. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. The diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Trypanosoma Brucei

DISEASE(S): Trypanosomiasis

SUBMITTER: Michael Urbaniak

LAB HEAD: Alan Fairlamb

PROVIDER: PXD002848 | Pride | 2015-11-25

REPOSITORIES: Pride

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Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome.

Jones Deuan C DC Foth Bernardo J BJ Urbaniak Michael D MD Patterson Stephen S Ong Han B HB Berriman Matthew M Fairlamb Alan H AH

PLoS neglected tropical diseases 20151218 12

SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of ...[more]

PMID: 26684831

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