title: Methods to assay inhibitors of tRNA synthetase activity.
abstract: Aminoacyl-tRNA synthetases (aa-RS) attracted interest as potential targets for new antibacterial compounds. Most organisms express 20 aa-RSs: one for each amino acid. Aa-RSs are essential proteins in all living organisms. When one aa-RS is inhibited, the corresponding tRNA is not charged and is therefore unavailable for translation. This leads to protein synthesis inhibition, which in turn causes cell growth arrest. Consequently, each compound that inhibits any of the aa-RS could be a potential antibacterial agent. Only one aa-RS inhibitor, the Ile-RS inhibitor mupirocin, is currently marketed as an antibacterial agent. We focused on phenylalanyl (Phe)-tRNA synthetase (Phe-RS), but the described methods are not restricted to Phe-RS and might be adapted to other aa-RS.
authors.affiliation: Bayer HealthCare AG, Wuppertal, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Beyer
authors.forename: Hein Peter
authors.initials: HP
authors.lastname: Kroll
authors.forename: Heike
authors.initials: H
authors.lastname: Brötz-Oesterhelt
mesh_terms: D000596:Amino Acids / Q000097:blood; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity; D002474:Cell-Free System; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D010652:Phenylalanine-tRNA Ligase / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D000604:Amino Acyl-tRNA Synthetases; D010652:Phenylalanine-tRNA Ligase