In a study published in Nature Communications on July 5th, 2024, a research team led by Prof. Gao Lizeng from the Chinese Academy of Sciences Institute of Biophysics suggested a bactericidal mechanism centered around nanozymes that simulate antimicrobial peptides (AMPs) and antimicrobial enzymes (AMEs) using biomimicry principles and developed a dual-functional high-efficiency antimicrobial nanozyme.
Antibacterial mechanism of Ni-IH-7 peptide nanozyme. Image Credit: Gao Lizeng’s group
The researchers used a variety of computational techniques, including Alphafold2, molecular dynamics simulation, and density functional theory, to optimize and choose a set of seven-peptide sequences, or IHIHICI, starting with the rational design of multi-peptide nanozymes.
These strategies were based on the essential amino acids in the active sites of AMPs and AMEs, such as histidine and cysteine, and combined peptide self-assembly and metal coordination principles.
The self-assembled nanozyme (AMPANs) exhibits targeted and effective fungicidal actions. It contains both AMP and AME functionalities.
Ni(Ac)2-assembled peptide nanotubes (Ni-IH-7) were chosen by the researchers as their study subjects. Ni-IH-7 has been shown through enzymatic assays to have peroxidase and phospholipase C-like activity.
The Ni-IH-7 peptide nanozyme demonstrated strong resistance to a range of hydrolytic enzymes as a result of the creation of a stable secondary structure nanotube.
Furthermore, they discovered that the Ni-IH-7 peptide nanozyme could specifically bind to the mannoprotein on the surface of Candida albicans and promote lipid peroxidation, resulting in iron death and hydrolysis of glycerophospholipids, therefore swiftly killing the fungi.
In vitro colony smear plate experiments on vaginal discharge from vaginitis patients demonstrated that the Ni-IH-7 peptide nanozyme exhibited effective antifungal properties that were not impaired by other components in the secretions.
This study is the first to suggest the method of combining antimicrobial peptides with nanozymes, creating peptide nanozymes from scratch using computer simulation, and methodically examining their unique mode of killing fungi. These findings will be helpful in the creation of new antimicrobial drugs.
Journal Reference:
Yuan, Y., et. al. (2024) Stable peptide-assembled nanozyme mimicking dual antifungal actions. Nature Communications. doi:10.1038/s41467-024-50094-6