The vancomycin-nisin(1-12) hybrid restores activity against vancomycin resistant enterococci

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

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)12661-12663
Number of pages3
JournalBiochemistry
Volume47
Issue number48
DOIs
StatePublished - 2 Dec 2008
Externally publishedYes

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