title: Aminoacyl-tRNA synthetase inhibitors as potential antibiotics.
abstract: Increasing resistance to antibiotics is a major problem worldwide and provides the stimulus for development of new bacterial inhibitors with preferably different modes of action. In search for new leads, several new bacterial targets are being exploited beside the use of traditional screening methods. Hereto, inhibition of bacterial protein synthesis is a long-standing validated target. Aminoacyl-tRNA synthetases (aaRSs) play an indispensable role in protein synthesis and their structures proved quite conserved in prokaryotes and eukaryotes. However, some divergence has occurred allowing the development of selective aaRS inhibitors. Following an outline on the action mechanism of aaRSs, an overview will be given of already existing aaRS inhibitors, which are largely based on mimics of the aminoacyl-adenylates, the natural reaction intermediates. This is followed by a discussion on more recent developments in the field and the bioavailability problem.
authors.affiliation: Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Minderbroedersstraat 10, BE-3000 Leuven, Belgium.
authors.forename: Gaston H M
authors.initials: GH
authors.lastname: Vondenhoff
authors.forename: Arthur
authors.initials: A
authors.lastname: Van Aerschot
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D000604:Amino Acyl-tRNA Synthetases