Identification of novel inhibitors of methionyl-tRNA synthetase (MetRS) by virtual screening.
Multiple inhibitors of the antibacterial target, Staphylococcus aureus MetRS, were identified by virtual screening. The process consisted of building a Catalyst pharmacophore from a ligand-S. aureus MetRS structure and using this pharmacophore to screen a commercial database. The top hits from this search were then docked into the S. aureus MetRS structure and this information was used to select compounds for testing. This resulted in a high hit rate of compounds that are in distinct structural classes from the known MetRS ligands.
Finn
John
J
Trius Therapeutics, R&D, 6310 Nancy Ridge Drive, Suite 101, San Diego, CA 92121, USA. jfinn@triusrx.com
Stidham
Mark
M
Hilgers
Mark
M
G C
Kedar
K
D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008024:Ligands; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000201:enzymology; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D008024:Ligands; D000604:Amino Acyl-tRNA Synthetases; D008718:Methionine-tRNA Ligase