title: A new set of assays for the discovery of aminoacyl-tRNA synthetase inhibitors.
abstract: Current biochemical methods available to monitor the activity of aminoacyl-tRNA synthetases (ARS) are ill-suited to high-throughput screening approaches for the identification of small-molecule inhibitors of these enzymes. In an attempt to improve the limitations of current assays we have developed a suite of new methods designed to streamline the discovery of new ARS antagonists. This set of assays includes approaches to monitor ARS activity in vitro, in human cells, and in bacteria. They are applicable to several ARSs from any given organism, can be easily adapted to very high-throughput set-ups, and allow for a multi-factorial selection of drug candidates.
authors.affiliation: Omnia Molecular S.L., c/ Baldiri Reixac 15-21, 08028 Barcelona, Catalonia, Spain.
authors.forename: Adélaïde
authors.initials: A
authors.lastname: Saint-Léger
authors.affiliation: Omnia Molecular S.L., c/ Baldiri Reixac 15-21, 08028 Barcelona, Catalonia, Spain; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, c/ Baldiri Reixac 10, 08028 Barcelona, Catalonia, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona, Catalonia, Spain. Electronic address: lluis.ribas@irbbarcelona.org.
authors.forename: Lluís
authors.initials: L
authors.lastname: Ribas de Pouplana
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D055808:Drug Discovery; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D055624:Methicillin-Resistant Staphylococcus aureus / Q000201:enzymology / Q000235:genetics; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*; D046249:Transfer RNA Aminoacylation
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D012345:RNA, Transfer, Amino Acid-Specific; D054852:Small Molecule Libraries; D008156:Luciferases; D000604:Amino Acyl-tRNA Synthetases
keywords: Aminoacyl-tRNA synthetase; Bioluminescence; Enzymatic assay; High-throughput screening; Luciferase; tRNA