抗菌剂
化学
赖氨酸
体内
肽
溶血
体外
抗菌肽
多重耐药
微生物学
细菌
药理学
生物化学
抗生素
氨基酸
生物
免疫学
生物技术
有机化学
遗传学
作者
Yu‐Chen Hu,Liang Hong,Rui Qu,Tong He,Xiaomin Tang,Wanyi Chen,Lixian Li,Hao Bai,Chao Li,Wei Wang,Gang Fu,Guangli Luo,Xuefeng Xia,Jinqiang Zhang
标识
DOI:10.1021/acs.jmedchem.1c01754
摘要
Cationic antimicrobial peptides (CAMPs) are promising for treatment of multidrug-resistant (MDR) bacteria-caused infections. However, clinical application of CAMPs has been hampered mostly due to their poor proteolytic stability and hemolytic toxicity. Recently, lysine-stapled CAMPs developed by us had been proved to increase peptide stability in vitro without induction of hemolysis. Herein, the applicability of the lysine stapling strategy was further explored by using five natural or artificial CAMPs as model peptides. Lysine stapling screening was implemented to provide 13 cyclic analogues in total. Biological screening of these cyclic analogues showed that CAMPs with a better amphiphilic structure were inclined to exhibit improved antimicrobial activity, protease stability, and biocompatibility after lysine-stapling. One of the stapled analogues of BF15-a1 was found to have extended half-life in plasma, enhanced antimicrobial activity against clinically isolated MDR ESKAPE pathogens, and remained highly effective in combating MRSA infection in a mouse model.
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