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Design and evaluation of tadpole-like conformational antimicrobial peptides.
- Source :
-
Communications Biology . 11/18/2023, Vol. 6 Issue 1, p1-14. 14p. - Publication Year :
- 2023
-
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]
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 6
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Communications Biology
- Publication Type :
- Academic Journal
- Accession number :
- 173724796
- Full Text :
- https://doi.org/10.1038/s42003-023-05560-0