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Discovery of Trypanosoma brucei inhibitors enabled by a unified synthesis of diverse sulfonyl fluorides

ABSTRACT: A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes were prepared, and then screened against Trypanosoma brucei. Four of the probes were found to have sub-micromolar anti-trypanosomal activity. A chemical proteomic approach, harnessing an alkynylated analogue and broad-spectrum fluorophosphonate tools, provided insights into the observed anti-trypanosomal activity, which likely stems from covalent modification of multiple protein targets.

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Trypanosoma Brucei

TISSUE(S): Cell Culture

SUBMITTER: Brian Suarez-Mantilla

LAB HEAD: Adam Nelson

PROVIDER: PXD056504 | Pride | 2024-10-16

REPOSITORIES: Pride

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	Readme-sampleIDs.xlsx	Xlsx
	Tb2598.d.zip	Other
	Tb2598.mzXML	Mzxml
	Tb2599.d.zip	Other
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