title: Synthesis and antibacterial activities of novel tyrocidine A glycosylated derivatives towards multidrug-resistant pathogens.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Hu
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006031:Glycosylation; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014440:Tyrocidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D014440:Tyrocidine
keywords: N-glycosylated peptide; antibacterial activity; antibiotic resistance; solid-phase peptide synthesis; tyrocidine A