[Polymer Chemistry] Cationic Peptidopolysaccharides Synthesized by ‘Click’ Chemistry with Enhanced Broad-Spectrum Antimicrobial Activities
作者：Yajuan Su, Liang Tian, Meng Yu, Qiang Gao, Dehui Wang, Yuewei Xi, Peng Yang, Bo Lei, Peter X. Ma, an
關鍵字：Peptidopolysaccharides, Antimicrobial, Click Chemistry
論文來源：期刊
具體來源：Polymer Chemistry
發表時間：2017年
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.