文献类型：期刊文献

英文题名：An Effective Strategy to Develop Potent and Selective Antifungal Agents from Cell Penetrating Peptides in Tackling Drug-Resistant Invasive Fungal Infections

作者：Wu, Yueming[1];Jiang, Weinan[1];Cong, Zihao[2];Chen, Kang[2];She, Yunrui[2];Zhong, Chao[2];Zhang, Wenjing[2];Chen, Minzhang[2];Zhou, Min[3];Shao, Ning[2];Xiao, Guohui[4];Shao, Xiaoyan[5];Dai, Yidong[5];Fei, Jian[4];Song, Gonghua[3];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,Sch Ma, Shanghai Frontier Sci Res Base Optogenet Tech Cel, Res Ctr Biomed Mat,Minist Educ,Key Lab Ultrafine, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[4]Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gen Surg, Sch Med, Shanghai 200025, Peoples R China;[5]Shanghai Ruijin Rehabil Hosp, Shanghai 200023, Peoples R China

年份：2022

卷号：65

期号：10

起止页码：7296

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000808007900019)】；

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 (No. 22075078, 21861162010), Program of Shanghai Academic/Technology Research Leader (20XD1421400), the China Postdoctoral Science Foundation (2021M701198), Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, grant 2021 Sci & Tech 03-28), and Research program of State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities (JKD01211520). The authors also thank Research Center of Analysis and Test of East China University of Science and Technology for help with characterization. We also thank the staff members of the Mass Spectrometry System at the National Facility for Protein Science in Shanghai (NFPS), Zhangjiang Lab, China for providing technical support and assistance in data collection and analysis.

语种：英文

摘要：The high mortality rate of invasive fungal infections and quick emergence of drug-resistant fungal pathogens urgently call for potent antifungal agents. Inspired by the cell penetrating peptide (CPP) octaarginine (R8), we elongated to 28 residues poly(d,l-homoarginine) to obtain potent toxicity against both fungi and mammalian cells. Further incorporation of glutamic acid residues shields positive charge density and introduces partial zwitterions in the obtained optimal peptide polymer that displays potent antifungal activity against drug-resistant fungi superior to antifungal drugs, excellent stability upon heating and UV exposure, negligible in vitro and in vivo toxicity, and strong therapeutic effects in treating invasive fungal infections. Moreover, the peptide polymer is insusceptible to antifungal resistance owing to the unique CPP-related antifungal mechanism of fungal membrane penetration followed by disruption of organelles within fungal cells. All these merits imply the effectiveness of our strategy to develop promising antifungal agents.