潜在的蝎形抗生素：万古霉素-TACzyme 偶联物对含脂质 II 的模型膜的靶向水解作用以及锌离子对其抗菌活性的调节

Potential scorpionate antibiotics: targeted hydrolysis of lipid II containing model membranes by vancomycin-TACzyme conjugates and modulation of their antibacterial activity by Zn-ions.

作者信息

Bauke Albada H, Arnusch Christopher J, Branderhorst Hilbert M, Verel Anne-Marie, Janssen Wouter T M, Breukink Eefjan, de Kruijff Ben, Pieters Roland J, Liskamp Rob M J

机构信息

Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

出版信息

Bioorg Med Chem Lett. 2009 Jul 15;19(14):3721-4. doi: 10.1016/j.bmcl.2009.05.064. Epub 2009 May 24.

DOI:10.1016/j.bmcl.2009.05.064

PMID:19524434

Abstract

The antibiotic vancomycin-that binds lipid II in the bacterial cell membrane-was conjugated to a mono- and tetravalent mimic of the tris-histidine catalytic triad of metalloenzymes. Targeted hydrolysis by the conjugate was observed using model membranes containing lipid II, and in vitro MIC-values of the targeted mimic constructs could be modulated by Zn-ions.

摘要

抗生素万古霉素（它能与细菌细胞膜中的脂质II结合）与金属酶三组氨酸催化三联体的单价和四价模拟物偶联。使用含有脂质II的模型膜观察到共轭物的靶向水解，并且靶向模拟构建体的体外最低抑菌浓度值可由锌离子调节。