文献类型：期刊文献

英文题名：Breaking or following the membrane-targeting mechanism: Exploring the antibacterial mechanism of host defense peptide mimicking poly(2-oxazoline)s

作者：Dai, Chengzhi[1];Zhou, Min[1];Jiang, Weinan[1];Xiao, Ximian[1];Zou, Jingcheng[1];Qian, Yuxin[1];Cong, Zihao[1];Ji, Zhemin[1];Liu, Longqiang[1];Xie, Jiayang[1];Qiao, Zhongqian[1];Liu, Runhui[1,2]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Mat Sci & Engn,Minist Educ, State Key Lab Bioreactor Engn,Key Lab Specially F, Shanghai 200237, Peoples R China;[2]Fudan Univ, State Key Lab Mol Engn Polymers, Shanghai 200438, Peoples R China

年份：2020

卷号：59

起止页码：220

外文期刊名：JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY

收录：;EI(收录号：20202808924189);WOS:【SCI-EXPANDED(收录号:WOS:000588638600022)】；

基金：This research was financially supported by the Natural Science Foundation of Shanghai (18ZR1410300), the National NaturalScience Foundation of China (No.21861162010, 21774031), theNational Key Research and Development Program of China (No. 2016YFC1100401), the Research Program of State Key Laboratoryof Bioreactor Engineering, the Fundamental Research Funds forthe Central Universities (No. 22221818014, 50321041917001). Theauthors thank the Research Center of Analysis and Test of EastChina University of Science and Technology for the help on thecharacterization. The authors also thank the staff members of theMass Spectrometry System at the National Facility for Protein Science (NFPS) for providing technical support and assistance in datacollection and analysis.

语种：英文

外文关键词：Poly(2-oxazoline); Host defense peptide; Antibacterial mechanism; Membrane-targeting; Antimicrobial resistance

摘要：Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo. Thus, functional peptide mimics have drawn a great deal of attention to address this challenge. Poly(2-oxazoline)s, a class of biocompatible and proteolysis-resistant polymer, can work as host defense peptide mimics without following the general membrane-targeting mechanism as shown in our previous work. This observation encouraged us to figure out if poly(2-oxazoline)s are special and break the general membrane-targeting mechanism of host defense peptides and their mimics. In this study, we aimed at the connection between structure and antibacterial mechanism of poly(2-oxazoline)s. A new gamma-aminobutyric acid (GABA)-pendent poly(2-oxazoline) was synthesized and investigated to compare with glycine-pendent poly(2-oxazoline) in our previous study, with the former polymer has two extra CH2 groups in the sidechain to increase the hydrophobicity and amphiphilicity. Membrane depolarization assay suggested that incorporating two more CH2 groups into the sidechain of poly(2-oxazoline) resulted in a mechanism switch from DNA-targeting to membrane-targeting, which was supported by the slow time-kill kinetics and slightly distorted and sunken membrane morphology. Besides, GABA-pendent poly(2-oxazoline) showed potent activity against methicillin-resistant S. aureus and low hemolysis on human red blood cells. Moreover, repeated use of the antimicrobial poly(2-oxazoline) did not stimulate bacteria to obtain resistance, which was an obvious advantage of membrane-targeting antimicrobial agents. (c) 2020 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.