Methods to assay inhibitors of tRNA synthetase activity.
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.
Beyer
Dieter
D
Bayer HealthCare AG, Wuppertal, Germany.
Kroll
Hein Peter
HP
Brötz-Oesterhelt
Heike
H
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
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D000604:Amino Acyl-tRNA Synthetases; D010652:Phenylalanine-tRNA Ligase