Design and Identification of Antimicrobial Peptoids Against the ESKAPE Pathogens

Abstract

A globalized health threat rises each year as pathogens quickly continue to develop modifications rendering previously prosperous antibiotics ineffective. Discovery or synthetically constructed antibacterial compounds are a necessary emphasis for new therapeutic options as there is currently a decline in drug discovery. While antimicrobial peptides are an intriguing option for antibiotic design; peptoids, which structurally contain the same backbone as peptides but with a slight modification, are better adapted to surviving degradation within the body. Combinatorial libraries were generated and optimization of peptoid design was further investigated to determine antibacterial efficiency against each pathogen in the ESKAPE panel. This study highlighted 6 combinatorial libraries with varied distribution of hydrophobic residues, overall charge ranging from a potential +1 to +7, and length varying from 3 to 7 residues long. Information gathered will guide future structure optimization for drug design aimed at Gram-negative pathogens. Antibacterial potency and mammalian toxicity were additionally determined for antibacterial peptoid K9 and compared with thiazole and oxazole K9 derivatives.