文献类型：期刊文献

英文题名：An effective approach to obtain functional poly-β-peptides for combating drug-resistant bacterial infections

作者：Chen, Sheng[1];Luo, Zhengjie[1];Zhou, Min[1,2];Xiao, Ximian[2];Cong, Zihao[2];Xie, Jiayang[2,3];Wu, Yueming[2];Zhang, Haodong[2];Zhao, Xuebin[2];Song, Gonghua[4];Liu, Runhui[1,2,3,5]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Frontiers Sci Ctr Materiobiol & Dynam Chem, Engn Res Ctr Biomed Mat,Minist Educ,Key Lab Ultraf, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Suzhou Inst Biomed Engn & Technol, Suzhou 215163, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[5]Shanghai Shyndec Pharmaceut Co Ltd, 378 Jian Lu Rd, Shanghai 201203, Peoples R China

年份：2025

卷号：13

期号：18

起止页码：5315

外文期刊名：JOURNAL OF MATERIALS CHEMISTRY B

收录：;EI(收录号：20251718275592);WOS:【SCI-EXPANDED(收录号:WOS:001465990000001)】；

基金：This research was supported by Shanghai "Science and Technology Innovation Action Plan" Computational Biology Program (24JS2830400), the National Natural Science Foundation of China (no. T2325010, 22305082, 22475069), National Key Research and Development Program of China (2024YFC2418700), the Fundamental Research Funds for the Central Universities (no. JKVD1251029, JKD01251701), Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission). The authors thank Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization for studies reviewed in this manuscript. Thanks for the support of the Analysis and Testing Center of School of Chemical Engineering, East China University of Science and Technology. We thank the staff members of the Integrated Laser Microscopy System at the National Facility for Protein Science in Shanghai (NFPS), Shanghai Advanced Research Institute, Chinese Academy of Sciences, China for sample preparation, data collection and analysis.

语种：英文

外文关键词：Chain length

摘要：The high mortality of drug-resistant bacterial infections, especially those caused by multidrug-resistant Gram-negative pathogens, highlights an urgent demand for promising antimicrobial strategies. Host defense peptide (HDP)-mimicking poly-beta-peptides have demonstrated significant potential in combating drug-resistant bacterial infections, with their antimicrobial activity closely dependent on their side-chain structures. However, the restricted structural diversity of poly-beta-peptides necessitates efficient synthetic methods to expand their diversity, particularly positively charged side-chain structures. This study presents a water-tolerant approach that facilitates the controllable synthesis of poly-beta-peptides with different chain lengths and structurally diverse side chains, including primary amines, tertiary amines, as well as alkyl, aryl, and methoxy groups. This approach serves as an HDP-mimicking discovery platform to obtain the optimal poly-beta-peptide, AOc0.8HNL0.2, which exhibits broad-spectrum antibacterial activity and high selectivity against drug-resistant bacteria. The antibacterial mechanism studies reveal that AOc0.8HNL0.2 disrupts the membrane of Gram-negative bacteria. In vivo evaluations substantiate the therapeutic potential of AOc0.8HNL0.2 in treating drug-resistant bacterial infections with no observable toxicity. This study underscores the potential of this convenient synthetic strategy as a promising platform for developing antimicrobial poly-beta-peptides to combat the growing threat of drug-resistant bacterial infections.