Designing and identifying β-hairpin peptide macrocycles with antibiotic potential.

ABSTRACT: Peptide macrocycles are a rapidly emerging class of therapeutic, yet the design of their structure and activity remains challenging. This is especially true for those with β-hairpin structure due to weak folding properties and a propensity for aggregation. Here, we use proteomic analysis and common antimicrobial features to design a large peptide library with macrocyclic β-hairpin structure. Using an activity-driven high-throughput screen, we identify dozens of peptides killing bacteria through selective membrane disruption and analyze their biochemical features via machine learning. Active peptides contain a unique constrained structure and are highly enriched for cationic charge with arginine in their turn region. Our results provide a synthetic strategy for structured macrocyclic peptid

SUBMITTER: Randall JR 

PROVIDER: S-EPMC9833666 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature