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Issue 25, 2017
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Cationic peptidopolysaccharides synthesized by ‘click’ chemistry with enhanced broad-spectrum antimicrobial activities

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Abstract

The emergence and spread of multidrug-resistant (MDR) bacteria is a serious clinical problem, and a challenge for the medical research community. There is an urgent need to explore novel effective antimicrobial molecules. Here, we report on a series of cationic peptidopolysaccharides that have a bacterial peptidoglycan-mimetic structure and have been synthesized using a facile thiol–ene ‘click’ chemistry to graft antimicrobial peptides, ε-poly-L-lysine (EPL), onto a polysaccharide (chitosan, CS) backbone. These CS-g-EPL copolymers demonstrated enhanced, selective, broad-spectrum antibacterial and antifungal activities towards Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), Gram-positive bacteria (Enterococcus faecalis and methicillin-resistant Staphylococcus aureus (MRSA)), and fungi (Candida albicans and Fusarium solani). Mechanistic studies proved that the CS-g-EPL likely disrupts the anionic microbial membrane leading to cell death, and is less likely to disrupt the mammalian cell membrane. In addition, CSL-g-EPL50% exhibits good in vitro biocompatibility with mammalian cells, and very little evidence of in vivo toxicity. Most importantly, CS-g-EPL demonstrated a strong antimicrobial efficacy with a log reduction of 4.66 in a rat MRSA infection model. These excellent biological properties present a promising prospect for CS-g-EPL in biomedical applications.

Graphical abstract: Cationic peptidopolysaccharides synthesized by ‘click’ chemistry with enhanced broad-spectrum antimicrobial activities

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Supplementary files

Article information


Submitted
29 Mar 2017
Accepted
05 May 2017
First published
08 May 2017

Polym. Chem., 2017,8, 3788-3800
Article type
Paper

Cationic peptidopolysaccharides synthesized by ‘click’ chemistry with enhanced broad-spectrum antimicrobial activities

Y. Su, L. Tian, M. Yu, Q. Gao, D. Wang, Y. Xi, P. Yang, B. Lei, P. X. Ma and P. Li, Polym. Chem., 2017, 8, 3788
DOI: 10.1039/C7PY00528H

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