The Vancomycin−Nisin(1−12) Hybrid Restores Activity against Vancomycin Resistant Enterococci

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• 作者：Christopher J. Arnusch ; Alexandre M. J. J. Bonvin ; Anne Marie Verel ; Wouter T. M. Jansen ; Rob M. J. Liskamp ; Ben de Kruijff ; Roland J. Pieters ; Eefjan Breukink
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：December 2, 2008
• 年：2008
• 卷：47
• 期：48
• 页码：12661-12663
• 全文大小：124K
• 年卷期：v.47,no.48(December 2, 2008)
• ISSN：1520-4995

文摘

Lipid II is a crucial component in bacterial cell wall synthesis [Breukink, E., et al. (1999) Science 286, 2361−2364]. It is the target of a number of important antibiotics, which include vancomycin and nisin [Breukink, E., and de Kruijff, B. (2006) Nat. Rev. Drug Discovery 5, 321−332]. Here we show that a hybrid antibiotic that consists of vancomycin and nisin fragments is significantly more active than the separate fragments against vancomycin resistant entercocci (VRE). Three different hybrids were synthesized using click chemistry and compared. Optimal spacer lengths and connection points were predicted using computer modeling.