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Covalent inhibitors : an opportunity for rational target selectivity

Published inCurrent opinion in chemical biology, vol. 39, p. 54-63
Publication date2017
Abstract

There is a resurging interest in compounds that engage their target through covalent interactions. Cysteine's thiol is endowed with enhanced reactivity, making it the nucleophile of choice for covalent engagement with a ligand aligning an electrophilic trap with a cysteine residue in a target of interest. The paucity of cysteine in the proteome coupled to the fact that closely related proteins do not necessarily share a given cysteine residue enable a level of unprecedented rational target selectivity. The recent demonstration that a lysine's amine can also be engaged covalently with a mild electrophile extends the potential of covalent inhibitors. The growing database of protein structures facilitates the discovery of covalent inhibitors while the advent of proteomic technologies enables a finer resolution in the selectivity of covalently engaged proteins. Here, we discuss recent examples of discovery and design of covalent inhibitors.

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Citation (ISO format)
LAGOUTTE, Roman, PATOURET, Rémi, WINSSINGER, Nicolas. Covalent inhibitors : an opportunity for rational target selectivity. In: Current opinion in chemical biology, 2017, vol. 39, p. 54–63. doi: 10.1016/j.cbpa.2017.05.008
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ISSN of the journal1367-5931
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Creation07/03/2017 10:51:00 AM
First validation07/03/2017 10:51:00 AM
Update time03/15/2023 1:49:10 AM
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