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- Title
Design and evaluation of tadpole-like conformational antimicrobial peptides.
- Authors
Tang, Ziyi; Jiang, Wuqiao; Li, Shuangli; Huang, Xue; Yang, Yi; Chen, Xiaorong; Qiu, Jingyi; Xiao, Chuyu; Xie, Ying; Zhang, Xu; Li, Jianguo; Verma, Chandra Shekhar; He, Yun; Yang, Aimin
- Abstract
Antimicrobial peptides are promising alternatives to conventional antibiotics. Herein, we report a class of "tadpole-like" peptides consisting of an amphipathic α-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 α-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 α-helical head and an aromatic tail activity. These exhibit potent antimicrobial activity, no hemolytic activity and cytotoxicity, and no propensity to induce resistance.
- Subjects
ANTIMICROBIAL peptides; PEPTIDE antibiotics; STRUCTURAL optimization; MOLECULAR dynamics; PEPTIDES; CYTOTOXINS; PEPTIDE amphiphiles
- Publication
Communications Biology, 2023, Vol 6, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-023-05560-0