The Journal of Antibiotics · 1997 · 23 citations · 25 references
PharmacyMedicinal ChemistryMolecular BiologyDrug DesignDrug DiscoveryStructural BiologyDrug-target Interaction MappingEnzyme InhibitionLigand BindingMolecular DockingPotency OptimizationVirtual ScreeningAntibiotic DiscoveryElongation Factor Tu FunctionStructure-based Screening
The development of a screen targeted to antibiotics which bind elongation factor Tu (EF-Tu) is described. The method was based on selection of antimicrobial activities which were antagonized by exogenous EF-Tu. Kirromycin, a known inhibitor of EF-Tu, was positive in this screen. Among 47,000 microorganisms screened, several producers of kirromycin-type antibiotics were detected and the novel antibiotics GE2270 and GE37468 were discovered. These thiopeptide molecules constitute, along with amithiamycin, a novel class of antibiotics acting on EF-Tu.
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