Arnusch Christopher J, Bonvin Alexandre M J J, Verel Anne Marie, Jansen Wouter T M, Liskamp Rob M J, de Kruijff Ben, Pieters Roland J, Breukink Eefjan
Department of Chemical Biology and Organic Chemistry, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Biochemistry. 2008 Dec 2;47(48):12661-3. doi: 10.1021/bi801597b.
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.
脂 II 是细菌细胞壁合成中的关键成分[Breukink, E., 等人 (1999) 《科学》286, 2361 - 2364]。它是多种重要抗生素的作用靶点，其中包括万古霉素和乳链菌肽[Breukink, E., 和 de Kruijff, B. (2006) 《自然综述：药物发现》5, 321 - 332]。在此我们表明，一种由万古霉素和乳链菌肽片段组成的杂合抗生素，相较于单独的片段，对耐万古霉素肠球菌（VRE）的活性显著更高。使用点击化学合成了三种不同的杂合体并进行比较。利用计算机建模预测了最佳间隔长度和连接点。
