Fabrication of Supramolecular Antibacterial Nanofibers with Membrane-Disruptive Mechanism

By studying the principles of self-assembly and combining the structural parameters required for the asymmetric distribution of antimicrobial peptides (AMPs), we newly designed and screened the high-activity and low-toxicity AMP F2I-LL. This peptide can form a supramolecular hydrogel with a nanofibe...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2021-11, Vol.64 (22), p.16480-16496
Main Authors: Chen, Tingting, Lyu, Yinfeng, Tan, Meishu, Yang, Chengyi, Li, Ying, Shao, Changxuan, Zhu, Yongjie, Shan, Anshan
Format: Article
Language:English
Subjects:
Amino Acids - chemistry
Animals
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Antimicrobial Peptides - chemistry
Antimicrobial Peptides - pharmacology
Cell Membrane - drug effects
Cells, Cultured
Gram-Negative Bacteria - drug effects
Gram-Positive Bacteria - drug effects
Hemolysis - drug effects
Humans
Mice
Microbial Sensitivity Tests
Nanofibers - chemistry
Protein Structure, Secondary
RAW 264.7 Cells
Swine
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Summary:By studying the principles of self-assembly and combining the structural parameters required for the asymmetric distribution of antimicrobial peptides (AMPs), we newly designed and screened the high-activity and low-toxicity AMP F2I-LL. This peptide can form a supramolecular hydrogel with a nanofiber microstructure in a simulated physiological environment (phosphate buffered saline), which exhibits broad-spectrum antibacterial activity. Compared with monomeric peptides, the introduction of a self-assembly strategy not only improved the bactericidal titer but also enhanced the serum stability of AMPs. Mechanistic studies showed that the positive charge enriched on the surface of the nanofiber was conducive to its rapid binding to the negatively charged part of the outer membrane of bacteria and further entered the inner membrane, increasing its permeability and ultimately leading to cell membrane rupture and death. This work provides insights into the design of nanopeptides with broad-spectrum antibacterial activity and provides new results for the development of biomedicine.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.1c00829