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Updated: Feb 12, 2026

A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
De novo identification of lipid II binding lipopeptides with antibacterial activity against vancomycin-resistant
Peter 't Hart1, Thomas M Wood1, Kamaleddin Haj Mohammad Ebrahim Tehrani1
1Department of Chemical Biology & Drug Discovery , Utrecht Institute for Pharmaceutical Sciences , Utrecht University , Universiteitsweg 99 , 3584 CG Utrecht , The Netherlands .
Abstract:
Creative strategies for identifying new antibiotics are essential to addressing the looming threat of a post-antibiotic era. We here report the use of a targeted peptide phage display screen as a means of generating novel antimicrobial lipopeptides. Specifically, a library of phage displayed bicyclic peptides was screened against a biomolecular target based on the bacterial cell wall precursor lipid II. In doing so we identified unique lipid II binding peptides that upon lipidation were found to be active against a range of Gram-positive bacteria including clinically relevant strains of vancomycin resistant bacteria. Optimization of the peptide sequence led to variants with enhanced antibacterial activity and reduced hemolytic activity. Biochemical experiments further confirm a lipid II mediated mode of action for these new-to-nature antibacterial lipopeptides.
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