Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers

作     者：Hui Liu Xiao Liu Yuan-Qiao Cao Ming Liu Miao-Miao Han Sheng-Xiang Ji Hui Liu;Xiao Liu;Yuan-Qiao Cao;Ming Liu;Miao-Miao Han;Sheng-Xiang Ji

作者机构：Key Laboratory of Polymer EcomaterialsChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology of ChinaHefei 230026China 

出 版 物：《Chinese Journal of Polymer Science》 (高分子科学（英文版）)

年 卷 期：2023年第41卷第3期

页      面：345-355,I0006页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0703[理学-化学] 

基　　金：financially supported by the National Natural Science Foundation of China(No.51973212) Department of Science and Technology of Jilin Province(Nos.20210203119SF and 20210203173SF)。 

主　　题：Hyperbranched random copolymers Lysine Hydrophobic amino acid Antibacterial activity High selectivity 

摘      要：Antimicrobial peptides(AMPs)have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance.Hyperbranched polylysine(HPL),an AMP mimics,has gained attention due to its broad-spectrum antibacterial activities,but it also suffers from high toxicity.Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine(K)with a hydrophobic amino acid,e.g.,alanine(A),tryptophan(W)or phenylalanine(F),to afford hyperbranched random copolymers.These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized.The G.mellonella infection model demonstrates that the copolymers are effective against the S.aureus infection in vivo.The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers.