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Title: Selective inhibition of an apicoplastic Aminoacyl-tRNA synthetase from Plasmodium falciparum
Author: Hoen, Rob
Novoa, Eva Maria
López, Alba
Camacho, Noelia
Cubells, Laia
Vieira, Pedro
Santos, Manuel
Marin-Garcia, Patricia
Bautista, Jose Maria
Cortés, Alfred
Ribas de Pouplana, Lluís
Royo, Miriam
Keywords: Aminoacyl-tRNA synthetases
Combinatorial chemistry
Drug design
Enzyme inhibitors
Molecular modeling
Issue Date: 2013
Publisher: Wiley-VCH Verlag
Abstract: The resistance of malaria parasites to available drugs continues to grow, and this makes the need for new antimalarial therapies pressing. Aminoacyl-tRNA synthetases (ARSs) are essential enzymes and well-established antibacterial targets and so constitute a promising set of targets for the development of new antimalarials. Despite their potential as drug targets, apicoplastic ARSs remain unexplored. We have characterized the lysylation system of Plasmodium falciparum, and designed, synthesized, and tested a set of inhibitors based on the structure of the natural substrate intermediate: lysyl-adenylate. Here we demonstrate that selective inhibition of apicoplastic ARSs is feasible and describe new compounds that that specifically inhibit Plasmodium apicoplastic lysyl-tRNA synthetase and show antimalarial activities in the micromolar range.
Peer review: yes
DOI: 10.1002/cbic.201200620
ISSN: 1439-4227
Appears in Collections:CESAM - Artigos
DBio - Artigos

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