title: Search for inhibitors of aminoacyl-tRNA synthases by virtual click chemistry.
abstract: The increase of multidrug-resistant strains of bacteria to known classes of antibiotics present a severe challenge for modern medicine. The most promising strategy to combat pathogenic bacteria is to discover new drug targets. In this regard, aminoacyl-tRNA synthetases are particularly well suited to develop novel drugs that show no cross-resistance to other classical antibiotics. To date various chemical structures that inhibit AA-RS have been identified. In this report we present an interesting approach towards generating of Leu-RS inhibitors by virtual click chemistry. That is we identified key fragments for ligand binding within catalytic pocket of Leu-RS, generated the collection of similar fragments with the use of Ligand.Info, identified the fragments that are most strongly bound in different areas within the catalytic pocket, and finally with the use of virtual click chemistry we generated a set of molecules which are most likely to act as highly potent bacterial Leu-RS inhibitors.
authors.affiliation: BioInfoBank Institute, Limanowskiego 24A, 60-744 Poznan, Poland. mmh@bioinfo.pl
authors.forename: Marcin
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Torchala
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D012356:RNA, Transfer, Leu / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D008024:Ligands; D012356:RNA, Transfer, Leu; D000604:Amino Acyl-tRNA Synthetases