Reengineering Antibiotics to Combat Bacterial Resistance: Click Chemistry [1,2,3]-Triazole Vancomycin Dimers with Potent Activity against MRSA and VRE
作者:Steven M. Silverman、John E. Moses、K. Barry Sharpless
DOI:10.1002/chem.201604765
日期:2017.1.1
worldwide concern, prompting the urgent development of new effective treatments for antibiotic resistant bacterial infections. Harnessing the benefits of multivalency and cooperativity against vancomycin‐resistant strains, we report a Click Chemistry approach towards reengineered vancomycin derivatives and the synthesis of a number of dimers with increased potency against MRSA and vancomycin resistant
万古霉素一直被认为是万不得已的药物。它在治疗多种耐药细菌感染,尤其是耐甲氧西林金黄色葡萄球菌(MRSA)方面的效率,对威胁生命的感染具有深远的影响。然而,对万古霉素的抗性的出现是引起全世界广泛关注的原因,这促使对抗生素抗性细菌感染的新的有效治疗方法的紧急开发。利用针对万古霉素抗性菌株的多重价和协同作用的优势,我们报道了针对重新设计的万古霉素衍生物的点击化学方法,以及合成了许多具有增强的抗MRSA和耐万古霉素肠球菌功效的二聚体(VRE; VanB)。通过强大的CuAAC反应,这些半合成的二聚体配体高效连接在一起,证明了高水平的选择性和纯度。