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Reengineering Antibiotics to Combat Bacterial Resistance: Click Chemistry [1,2,3]‐Triazole Vancomycin Dimers with Potent Activity against MRSA and VRE
Author(s) -
Silverman Steven M.,
Moses John E.,
Sharpless K. Barry
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201604765
Subject(s) - click chemistry , vancomycin , triazole , microbiology and biotechnology , antibiotics , business process reengineering , chemistry , staphylococcus aureus , biology , combinatorial chemistry , bacteria , genetics , organic chemistry , oil refinery
Vancomycin has long been considered a drug of last resort. Its efficiency in treating multiple drug‐resistant bacterial infections, particularly methicillin‐resistant Staphylococcus aureus (MRSA), has had a profound effect on the treatment of life‐threatening infections. However, the emergence of resistance to vancomycin is a cause for significant 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 Enterococci (VRE; VanB). These semi‐synthetic dimeric ligands were linked together with great efficiency using the powerful CuAAC reaction, demonstrating high levels of selectivity and purity.