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However, this situation is under threat because of the increasing appearance of vancomycin\u2010resistant bacteria (VRB). Herein, we report a series of novel vancomycin derivatives carrying a sulfonium moiety. The sulfonium\u2013vancomycin derivatives exhibited enhanced antibacterial activity against VRB both in\u2005vitro and in\u2005vivo. These derivatives also exhibited activity against some Gram\u2010negative bacteria. The sulfonium modification enhanced the interaction of vancomycin with the bacterial cell membrane and disrupts membrane integrity. Furthermore, the in\u2005vivo pharmacokinetic profile, stability, and toxicity of these derivatives demonstrated good druggability of the sulfonium\u2013vancomycin analogues. This work provides a promising strategy for combating drug\u2010resistant bacterial infection, and advances the knowledge on sulfonium derivatives for structural optimization and drug development.<\/jats:p>","DOI":"10.1002\/anie.201902210","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T17:45:01Z","timestamp":1553535901000},"page":"6678-6682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Sulfonium, an Underestimated Moiety for Structural Modification, Alters the Antibacterial Profile of Vancomycin Against Multidrug\u2010Resistant Bacteria"],"prefix":"10.1002","volume":"58","author":[{"given":"Dongliang","family":"Guan","sequence":"first","affiliation":[{"name":"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 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