1. Design and evaluation of tadpole-like conformational antimicrobial peptides.
- Author
-
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, and Yang, Aimin
- Subjects
ANTIMICROBIAL peptides ,PEPTIDE antibiotics ,STRUCTURAL optimization ,MOLECULAR dynamics ,PEPTIDES ,CYTOTOXINS ,PEPTIDE amphiphiles - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF