文献类型：期刊文献

英文题名：Microbial Metabolite Inspired β-Peptide Polymers Displaying Potent and Selective Antifungal Activity

作者：Zhang, Donghui[1];Shi, Chao[2];Cong, Zihao[2];Chen, Qi[2];Bi, Yufang[2];Zhang, Junyu[2];Ma, Kaiqian[2];Liu, Shiqi[2];Gu, Jiawei[2];Chen, Minzhang[2];Lu, Ziyi[2];Zhang, Haodong[2];Xie, Jiayang[2];Xiao, Ximian[2];Liu, Longqiang[2];Jiang, Weinan[2];Shao, Ning[2];Chen, Sheng[2];Zhou, Min[1];Shao, Xiaoyan[3];Dai, Yidong[3];Li, Maoquan[4];Zhang, Lixin[1];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, Sch Mat Sci & Engn, Frontiers Sci Ctr Materiobiol & Dynam Chem, Key Lab Ultrafine Mat,Minist Educ,Res Ctr Biomed, Shanghai 200237, Peoples R China;[3]Shanghai Ruijin Rehabil Hosp, Shanghai 200023, Peoples R China;[4]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Intervent & Vasc Surg,Shanghai Clin Res Ctr, Shanghai 200072, Peoples R China

年份：2022

卷号：9

期号：14

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20221211813574);WOS:【SCI-EXPANDED(收录号:WOS:000776179100001)】；

基金：The authors thank Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization. This research was supported by the National Natural Science Foundation of China (No. 22075078, 21861162010), the National Natural Science Foundation of China for Innovative Research Groups (No. 51621002), Program of Shanghai Academic/Technology Research Leader (20XD1421400), Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism grant 2021 Sci & Tech 03-28 (Shanghai Municipal Education Commission), Research program of State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities (JKD01211520). All animal procedures were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of the Shanghai Tenth People's Hospital (License number: SYXK-2021-0012), and experiments were approved by the Animal Ethics Committee of the Shanghai Tenth People's Hospital, Tongji University School of Medicine (Accreditation number of the laboratory: SHDSYY-2021-1729).

语种：英文

外文关键词：antifungal agents; fungal keratitis; host defense peptide mimicking; poly(DL-diaminopropionic acid); beta-peptide polymers

摘要：Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL-diaminopropionic acid) (PDAP) from the ring-opening polymerization of beta-amino acid N-thiocarboxyanhydrides, by mimicking c-poly-lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. The optimal PDAP displays potent antifungal activity with minimum inhibitory concentration as low as 0.4 mu g mL(-1) against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits the formation of fungal biofilms and eradicates the mature biofilms. In vivo studies show that PDAP is safe and effective in treating fungal keratitis, which suggests PDAPs as promising new antifungal agents.