Scientific article
Open access

Covalent inhibitors : an opportunity for rational target selectivity

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

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.

Research group
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
Main files (2)
Article (Published version)
Article (Accepted version)
ISSN of the journal1367-5931

Technical informations

Creation07/03/2017 10:51:00 AM
First validation07/03/2017 10:51:00 AM
Update time03/15/2023 1:49:10 AM
Status update03/15/2023 1:49:09 AM
Last indexation01/17/2024 12:15:14 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack