Extended targeting potential and improved synthesis of Microcin C analogs as antibacterials |
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Authors: | Vondenhoff Gaston H M Dubiley Svetlana Severinov Konstantin Lescrinier Eveline Rozenski Jef Van Aerschot Arthur |
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Institution: | Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. |
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Abstract: | Microcin C (McC) (1) is a potent antibacterial compound produced by some Escherichia coli strains. McC functions through a Trojan-Horse mechanism: it is actively taken up inside a sensitive cell through the function of the YejABEF-transporter and then processed by cellular aminopeptidases. Processed McC (2) is a non-hydrolysable aspartyl-adenylate analog that inhibits aspartyl-tRNA synthetase (AspRS). A new synthesis is described that allows for the production of a wide variety of McC analogs in acceptable amounts. Using this synthesis a number of diverse compounds was synthesized with altered target specificity. Further characteristics of the YejABEF transporters were determined using these compounds. |
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