title: The antimicrobial natural product chuangxinmycin and some synthetic analogues are potent and selective inhibitors of bacterial tryptophanyl tRNA synthetase.
abstract: The antimicrobial natural product chuangxinmycin has been found to be a potent and selective inhibitor of bacterial tryptophanyl tRNA synthetase (WRS). A number of analogues have been synthesised. The interaction with WRS appears to be highly constrained, as only sterically smaller analogues afforded significant inhibition. The only analogue to show inhibition comparable to chuangxinmycin also had antibacterial activity. WRS inhibition may contribute to the antibacterial action of chuangxinmycin.
authors.affiliation: GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
authors.forename: Murray J
authors.initials: MJ
authors.lastname: Brown
authors.forename: Paul S
authors.initials: PS
authors.lastname: Carter
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Fenwick
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fosberry
authors.forename: Dieter W
authors.initials: DW
authors.lastname: Hamprecht
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hibbs
authors.forename: Richard L
authors.initials: RL
authors.lastname: Jarvest
authors.forename: Lucy
authors.initials: L
authors.lastname: Mensah
authors.forename: Peter H
authors.initials: PH
authors.lastname: Milner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Hanlon
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pope
authors.forename: Christine M
authors.initials: CM
authors.lastname: Richardson
authors.forename: Andrew
authors.initials: A
authors.lastname: West
authors.forename: David R
authors.initials: DR
authors.lastname: Witty
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006868:Hydrolysis; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014369:Tryptophan-tRNA Ligase / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007211:Indoles; C014414:chuangxinmycin; D014369:Tryptophan-tRNA Ligase