Natural product derivatives with bactericidal activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis |
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Authors: | Joshua B Phillips Adrienne E Smith Brian R Kusche Bradley A Bessette P Whitney Swain Stephen C Bergmeier Mark C McMills Dennis L Wright Nigel D Priestley |
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Institution: | 1. Department of Chemistry, University of Montana, Missoula, MT 59812, USA;2. Promiliad Biopharma Inc., 950 West Fork Petty Creek Road, Alberton, MT 59820, USA |
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Abstract: | We have shown that the intentional engineering of a natural product biosynthesis pathway is a useful way to generate stereochemically complex scaffolds for use in the generation of combinatorial libraries that capture the structural features of both natural products and synthetic compounds. Analysis of a prototype library based upon nonactic acid lead to the discovery of triazole-containing nonactic acid analogs, a new structural class of antibiotic that exhibits bactericidal activity against drug resistant, Gram-positive pathogens including Staphylococcus aureus and Enterococcus faecalis. |
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