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Title

Synthesis and Biological Evaluation of Vancomycin Dimers with Potent Activity against Vancomycin-Resistant Bacteria: Target-Accelerated Combinatorial Synthesis

Authors
Nicolaou, K. C.
Hughes, Robert
Cho, Suk Young
Labischinski, Harald
Endermann, Rainer
Published in Chemistry - A European Journal. 2001, vol. 7, no. 17, p. 3824-3843
Abstract Based on the notion that dimerization and/or variation of amino acid 1 of vancomycin could potentially enhance biological activity, a series of synthetic and chemical biology studies were undertaken in order to discover potent antibacterial agents. Herein we describe two ligation methods (disulfide formation and olefin metathesis) for dimerizing vancomycin derivatives and applications of target-accelerated combinatorial synthesis (e.g. combinatorial synthesis in the presence of vancomycin's target Ac2-l-Lys-d-Ala-d-Ala) to generate libraries of vancomycin dimers. Screening of these compound libraries led to the identification of a number of highly potent antibiotics effective against vancomycin-suspectible, vancomycin-intermediate resistant and, most significantly, vancomycin-resistant bacteria.
Keywords antibioticsbiological evaluationcombinatorial synthesissynthesis designvancomycin
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NICOLAOU, K. C. et al. Synthesis and Biological Evaluation of Vancomycin Dimers with Potent Activity against Vancomycin-Resistant Bacteria: Target-Accelerated Combinatorial Synthesis. In: Chemistry - A European Journal, 2001, vol. 7, n° 17, p. 3824-3843. https://archive-ouverte.unige.ch/unige:24438

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Deposited on : 2012-12-12

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