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Design and evaluation of tadpole-like conformational antimicrobial peptides
Tang, Ziyi1,2; Jiang, Wuqiao3; Li, Shuangli4; Huang, Xue3; Yang, Yi3; Chen, Xiaorong3; Qiu, Jingyi1; Xiao, Chuyu3; Xie, Ying3; Zhang, Xu4
2023-11-18
摘要Antimicrobial peptides are promising alternatives to conventional antibiotics. Herein, we report a class of "tadpole-like" peptides consisting of an amphipathic alpha-helical head and an aromatic tail. A structure-activity relationship (SAR) study of "tadpole-like" temporin-SHf and its analogs revealed that increasing the number of aromatic residues in the tail, introducing Arg to the alpha-helical head and rearranging the peptide topology dramatically increased antimicrobial activity. Through progressive structural optimization, we obtained two peptides, HT2 and RI-HT2, which exhibited potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance. NMR and molecular dynamics simulations revealed that both peptides indeed adopted "tadpole-like" conformations. Fluorescence experiments and electron microscopy confirmed the membrane targeting mechanisms of the peptides. Our studies not only lead to the discovery of a series of ultrashort peptides with potent broad-spectrum antimicrobial activities, but also provide a new strategy for rational design of novel "tadpole-like" antimicrobial peptides. Here, through progressive structural optimization, two "tadpole-like" antimicrobial peptides are constructed with an amphipathic alpha-helical head and an aromatic tail activity. These exhibit potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance.
DOI10.1038/s42003-023-05560-0
发表期刊COMMUNICATIONS BIOLOGY
卷号6期号:1页码:14
通讯作者He, Yun(yun.he@cqu.edu.cn) ; Yang, Aimin(aimin.yang@cqu.edu.cn)
收录类别SCI
WOS记录号WOS:001107676500004
语种英语