文献类型：期刊文献

英文题名：Secondary Amine Pendant β-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis

作者：Qian, Yuxin[1];Deng, Shuai[2];Cong, Zihao[2];Zhang, Haodong[2];Lu, Ziyi[2];Shao, Ning[2];Bhatti, Sonia Abid[2];Zhou, Cong[3];Cheng, Jiagao[3];Gellman, Samuel H.[4];Liu, Runhui[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Me, Res Ctr Biomed Mat Minist Educ, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[4]Univ Wisconsin, Dept Chem, Madison, WI 53706 USA

年份：2022

卷号：144

期号：4

起止页码：1690

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20220711632212);WOS:【SCI-EXPANDED(收录号:WOS:000744685100001)】；

基金：This research was supported by the National Natural Science Foundation of China for Innovative Research Groups (no. 51621002), the National Natural Science Foundation of China (nos. 21574038, 22075078, 21861162010), Program of Shanghai Academic/Technology Research Leader (20XD1421400), Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, grant 2021 Sci & Tech 0328), and Research program of State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities (JKD01211520). Work at UWMadison was supported in part by the U.S. National Science Foundation (CHE-1904940). The authors also thank Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization.

语种：英文

外文关键词：Amines - Antibiotics - Cytotoxicity - Amino acids - Functional polymers

摘要：Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking beta-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial beta-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.