Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Synthesis and Antibiotic Activity of Chitosan-Based Comb-Like Co-Polypeptides

Version 1 : Received: 9 March 2023 / Approved: 10 March 2023 / Online: 10 March 2023 (08:57:12 CET)

A peer-reviewed article of this Preprint also exists.

Enright, T.P.; Garcia, D.L.; Storti, G.; Heindl, J.E.; Sidorenko, A. Synthesis and Antibiotic Activity of Chitosan-Based Comb-like Co-Polypeptides. Mar. Drugs 2023, 21, 243. Enright, T.P.; Garcia, D.L.; Storti, G.; Heindl, J.E.; Sidorenko, A. Synthesis and Antibiotic Activity of Chitosan-Based Comb-like Co-Polypeptides. Mar. Drugs 2023, 21, 243.

Abstract

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

Keywords

Antimicrobial peptides; Chitosan; comb-like co-polypeptide; N-carboxyanhydrides; ring-opening polymerization

Subject

Chemistry and Materials Science, Medicinal Chemistry

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