CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Center for Biotherapeutics Discovery Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, PR China.
CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Center for Biotherapeutics Discovery Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China; Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang, Hunan 421001, China.
Bioorg Med Chem Lett. 2021 Aug 1;45:128122. doi: 10.1016/j.bmcl.2021.128122. Epub 2021 May 17.
Developing novel antibiotics is urgently needed with emergency of drug resistance. Vancomycin, the last resort for intractable Gram-positive bacterial infections, is ineffective against Gram-negative bacteria and vancomycin resistant bacteria. Herein, we report a series of novel vancomycin derivatives carrying LPS binding peptides, vancomycin-LPS binding peptide conjugates (VPCs). The LPS binding peptides were conjugated onto 4 sites of vancomycin via CuAAC or maleimide- sulfydryl addition, and the formed VPCs were screened against VISA/VRE and Gram-negative strains. VPCs exhibited enhanced activity against vancomycin resistant bacteria and obtained the activity against Gram-negative bacteria in vitro, providing a novel strategy for vancomycin modification and glycopeptide antibiotics synthesis.
由于耐药性的出现，急需开发新型抗生素。万古霉素是治疗耐药革兰阳性菌感染的最后手段，但对革兰氏阴性菌和万古霉素耐药菌无效。在此，我们报告了一系列携带脂多糖结合肽的新型万古霉素衍生物，即万古霉素-脂多糖结合肽缀合物（VPC）。通过 CuAAC 或马来酰亚胺-巯基加成将脂多糖结合肽连接到万古霉素的 4 个位点上，并筛选出对 VISA/VRE 和革兰氏阴性菌具有活性的 VPC。VPC 对万古霉素耐药菌的活性增强，并在体外获得了对革兰氏阴性菌的活性，为万古霉素修饰和糖肽抗生素合成提供了一种新策略。
