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Antibiotic optimization via in vitro glycorandomization.

Xun Fu·Christoph Albermann·Jiqing Jiang·Jianchun Liao·Changsheng Zhang·Jon S Thorson
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Abstract

In nature, the attachment of sugars to small molecules is often used to mediate targeting, mechanism of action and/or pharmacology. As an alternative to pathway engineering or total synthesis, we report a useful method, in vitro glycorandomization (IVG), to diversify the glycosylation patterns of complex natural products. We have used flexible glycosyltransferases on nucleotide diphosphosugar (NDP-sugar) libraries to generate glycorandomized natural products and then applied chemoselective ligation to produce monoglycosylated vancomycins that rival vancomycin.

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Anti-Bacterial AgentsCarbohydratesCombinatorial Chemistry TechniquesGlycosylationGlycosyltransferasesPeptide LibraryProtein Interaction MappingQuality ControlVancomycinJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Xun Fu, Christoph Albermann, Jiqing Jiang, Jianchun Liao, Changsheng Zhang, Jon S Thorson. 2003-11-09. Antibiotic optimization via in vitro glycorandomization.. https://doi.org/10.1038/nbt909

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