Cyclic Poly(α-amino acid) Quaternary Ammonium Salt with Potent Antibacterial Activity and Low Toxicity

作者：G. H. Gao, Wenlong Zhang, Yongchang Tian, Tingting Hua, Pengqi Wan, Chunsheng Xiao, Xuesi Chen · 发表于：Biomacromolecules · 年份：2025 · DOI：10.1021/acs.biomac.5c00407 · 被引用次数：12 · 研究领域：Antimicrobial agents and applications、Biopolymer Synthesis and Applications、Synthesis and Characterization of Heterocyclic Compounds

Cationic antibacterial polymers have been extensively investigated as alternatives to antibiotics to address the challenges of antibiotic-resistant bacteria. However, their inevitable cytotoxicity significantly restricts their practical application. Cyclization strategies provide a reference for solving this dilemma. In this study, we designed and synthesized a series of cyclic cationic poly(α-amino acid) quaternary ammonium salts with potent antibacterial activity and low toxicity. Notably, the optimal polymer, c PCHLG 10 -C 8, demonstrated remarkable antibacterial activity coupled with low cytotoxicity, exhibiting a selectivity index (SI = 128) against S. aureus that was 8-fold higher than the corresponding linear structure l PCHLG 10 -C 8 (SI = 16). Circular dichroism spectroscopy results indicated that the cyclic structure contributed to reduced cytotoxicity by diminishing the degree of α-helix conformation. Additionally, c PCHLG 10 -C 8 displayed rapid bactericidal properties, negligible propensity to induce bacterial resistance, and effectively inhibited or cleared bacterial biofilms. Furthermore, in a mouse epidermal wound infection model, c PCHLG 10 -C 8 showed outstanding in vivo antibacterial effects. Hence, this study offers a promising approach for designing cationic polymers that balance antimicrobial activity and biocompatibility.