The antimicrobial natural product chuangxinmycin and some synthetic analogues are potent and selective inhibitors of bacterial tryptophanyl tRNA synthetase.
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.
Brown
Murray J
MJ
GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
Carter
Paul S
PS
Fenwick
Ashley S
AS
Fosberry
Andrew P
AP
Hamprecht
Dieter W
DW
Hibbs
Martin J
MJ
Jarvest
Richard L
RL
Mensah
Lucy
L
Milner
Peter H
PH
O'Hanlon
Peter J
PJ
Pope
Andrew J
AJ
Richardson
Christine M
CM
West
Andrew
A
Witty
David R
DR
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*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007211:Indoles; C014414:chuangxinmycin; D014369:Tryptophan-tRNA Ligase