CRISPR-based oligo recombineering prioritizes apicomplexan cysteines for drug discovery.

ABSTRACT: Nucleophilic amino acids are important in covalent drug development yet underutilized as anti-microbial targets. Chemoproteomic technologies have been developed to mine chemically accessible residues via their intrinsic reactivity towards electrophilic probes but cannot discern which chemically reactive sites contribute to protein function and should therefore be prioritized for drug discovery. To address this, we have developed a CRISPR-based oligo recombineering (CORe) platform to support the rapid identification, functional prioritization and rational targeting of chemically reactive sites in haploid systems. Our approach couples protein sequence and function with biological fitness of live cells. Here we profile the electrophile sensitivity of proteinogenic cysteines in the eukaryotic

SUBMITTER: Benns HJ 

PROVIDER: S-EPMC9613468 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature