title: Extended targeting potential and improved synthesis of Microcin C analogs as antibacterials.
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.
authors.affiliation: Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Gaston H M
authors.initials: GH
authors.lastname: Vondenhoff
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dubiley
authors.forename: Konstantin
authors.initials: K
authors.lastname: Severinov
authors.forename: Eveline
authors.initials: E
authors.lastname: Lescrinier
authors.forename: Jef
authors.initials: J
authors.lastname: Rozenski
authors.forename: Arthur
authors.initials: A
authors.lastname: Van Aerschot
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001430:Bacteriocins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C020411:microcin