Design, synthesis, and antibacterial evaluation of vancomycin-LPS binding peptide conjugates. (1st August 2021)

• Record Type: Journal Article
• Authors: Shi, Weiwei; Chen, Feifei; Zou, Xiangman; Jiao, Shang; Wang, Siqi; Hu, Yu; Lan, Lefu; Tang, Feng; Huang, Wei
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 45(2021)
• Publication Date: 2021-08-01
• Subjects: Vancomycin analogues -- LPS binding peptides -- Vancomycin-Peptide Conjugates -- Antibacterial activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128122
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Developing novel antibiotics is urgently needed with emergency of drug resistance. Vancomycin, the last resort for intractable Gram-positive bacterial infections, is ineffective against Gram-negative bacteria and vancomycin resistant bacteria. Herein, we report a series of novel vancomycin derivatives carrying LPS binding peptides, vancomycin-LPS binding peptide conjugates (VPCs). The LPS binding peptides were conjugated onto 4 sites of vancomycin via CuAAC or maleimide- sulfydryl addition, and the formed VPCs were screened against VISA/VRE and Gram-negative strains. VPCs exhibited enhanced activity against vancomycin resistant bacteria and obtained the activity against Gram-negative bacteria in vitro, providing a novel strategy for vancomycin modification and glycopeptide antibiotics synthesis.