Toolkit of Approaches To Support Target-Focused Drug Discovery for <i>Plasmodium falciparum</i> Lysyl tRNA Synthetase.

ABSTRACT: There is a pressing need for new medicines to prevent and treat malaria. Most antimalarial drug discovery is reliant upon phenotypic screening. However, with the development of improved target validation strategies, target-focused approaches are now being utilized. Here, we describe the development of a toolkit to support the therapeutic exploitation of a promising target, lysyl tRNA synthetase (PfKRS). The toolkit includes resistant mutants to probe resistance mechanisms and on-target engagement for specific chemotypes; a hybrid KRS protein capable of producing crystals suitable for ligand soaking, thus providing high-resolution structural information to guide compound optimization; chemical probes to facilitate pulldown studies aimed at revealing the full range of specifically int

SUBMITTER: Milne R 

PROVIDER: S-EPMC9469095 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature