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

被引：77

作者：

Arnusch, Christopher J. ^{[1
,2
]}

Bonvin, Alexandre M. J. J. ^{[3
]}

Verel, Anne Marie ^{[4
]}

Jansen, Wouter T. M. ^{[4
]}

Liskamp, Rob M. J. ^{[1
]}

de Kruijff, Ben ^{[2
]}

Pieters, Roland J. ^{[1
]}

Breukink, Eefjan ^{[2
]}

机构：

[1] Univ Utrecht, Dept Med Chem & Chem Biol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands

[2] Univ Utrecht, Dept Chem Biol & Organ Chem, Inst Biomembranes, NL-3584 CH Utrecht, Netherlands

[3] Univ Utrecht, Dept NMR Spect, Bijvoet Ctr Biomol Res, Fac Sci, NL-3584 CH Utrecht, Netherlands

[4] Univ Med Ctr Utrecht, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands

来源：

BIOCHEMISTRY | 2008年 / 47卷 / 48期

关键词：

D O I：

10.1021/bi801597b

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：12661 / 12663

页数：3

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