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The antimicrobial natural product chuangxinmycin and some synthetic analogues are potent and selective inhibitors of bacterial tryptophanyl tRNA synthetase
Authors:Brown Murray J  Carter Paul S  Fenwick Ashley S  Fosberry Andrew P  Hamprecht Dieter W  Hibbs Martin J  Jarvest Richard L  Mensah Lucy  Milner Peter H  O'Hanlon Peter J  Pope Andrew J  Richardson Christine M  West Andrew  Witty David R
Affiliation:GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
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.
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