Approaching novel antibiotic targets using peptidomimetics

This thesis presents a comprehensive study of constrained peptides as novel bioactive agents with antibiotic properties, focusing on their design, mechanism of action, and potential in combating antibiotic-resistant bacteria. It introduces two distinct series of constrained peptides, each with unique antibiotic activities and modes of action. The first series non-specifically alters the permeability of the outer membrane in Gram-negative bacteria, enabling synergistic effects with other antibiotics. The second series targets a specific protein-protein interaction (PPI) in the bacterial divisome, inhibiting cell division through a covalent mode of action. Notably, their combined application shows synergy in vivo. Furthermore, the methodologies and insights gained from this work offer valuable guidance for future research in peptide-based antibiotic development.