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Synthesis and antibacterial activities of novel tyrocidine A glycosylated derivatives towards multidrug‐resistant pathogens
Author(s) -
Zou Yan,
Zhao Qingjie,
Zhang Chunmei,
Wang Liang,
Li Wenjuan,
Li Xiang,
Wu Qiuye,
Hu Honggang
Publication year - 2015
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2774
Subject(s) - glycopeptide , glycosylation , antibacterial activity , chemistry , antibiotics , peptide , glycan , multiple drug resistance , combinatorial chemistry , biochemistry , microbiology and biotechnology , biology , bacteria , glycoprotein , genetics
Glycosylation can have a multifaceted impact on the properties and functions of peptides and plays a critical role in interacting with or binding to the target molecules. Herein, based on the previously reported method for macrocyclic glycopeptide synthesis, two series of tyrocidine A glycosylated derivatives ( 1a–f and 2a–f ) were synthesized and evaluated for their antibacterial activities to further study the structure and activity relationships (SAR). Biological studies showed that the synthetic glycosylated derivatives had good antibacterial activities towards methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant Enterococcus . SAR studies based on various glycans and linkages were used to enhance the biochemical profile, resulting in the identification of several potent antibiotics, such as 1f , with a great improved therapeutic index than tyrocidine A. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.