A5071948445- Bacteriophages and microbial interactions
- Antimicrobial Peptides and Activities
- Chemical Synthesis and Analysis
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Synthesis and biological activity
- Click Chemistry and Applications
Bicycle Therapeutics (United Kingdom)
2022-2024
Abstract Penicillin binding proteins (PBPs) are well validated antimicrobial targets, but the prevalence of β-lactamase driven resistance and, more rarely, target-based mutations, necessitates new classes PBP-targeting drugs. Here we describe discovery and optimisation novel, bicyclic peptide (Bicycle ® ) inhibitors E. coli PBP3 ( Ec PBP3) using a proprietary phage display platform, their conjugation to linear peptides confer outer membrane permeation. These molecules exhibited high-affinity...
Growing antibiotic resistance is rapidly threatening the efficacy of treatments for Gram-negative infections. Bicycle molecules, constrained bicyclic peptides from diverse libraries generated by bacteriophage display that bind with high affinity to a chosen target are potential new class antibiotics. The generally impermeable bacterial outer membrane currently limits access bacteria. conjugation active offers an avenue penetration. Here, we investigate which physicochemical properties...