Work

Utilizing Proteolytic‐Resistant Nano‐Short Peptide Based on Naphthyl Tail‐Anchored to Combat Bacterial Infections

Year: 2025

Type: article

Abstract: The extensive application of antimicrobial peptides (AMPs) as viable alternatives to antibiotics is constrained by their high susceptibility to enzymatic degradation by proteases. In this study, a series of potent nano‐short peptides are engineered based on the short peptide anti‐enzymolysis motif “R D RRP” by introducing different hydrophobic groups using different strategies. The validity of the self‐assembly system triggered by naphthyl tail anchoring is confirmed through a comprehensive analysis of the bioactivity and nanoproperties of these nano‐short peptides. The naphthyl tail‐anchored N 4 peptide (Nal‐Nal‐Nal‐Nal‐R D ‐R‐R‐P) could self‐assemble into nanofibers in aqueous solutions, exhibiting potent and broad‐spectrum antimicrobial activity with excellent biocompatibility (Geometric Mean of the Minimum Inhibitory Concentration (GM MIC ) = 5.04, Geometric Mean of the Selectivity Index (GM SI ) = 50.8) and remarkable biostability against physiological challenges (salt concentrations, serum components, and various proteases). More importantly, the low resistance propensity for N 4 is attributed to multiple antimicrobial mechanisms combining physical membrane‐breaking and energy metabolism disruption. Its efficacy is substantiated in both Escherichia coli ( E. coli ) induced murine peritonitis‐sepsis and Methicillin‐Resistant Staphylococcus aureus ( MRSA) mediated skin infection models in mice. In summary, these findings advance the design of AMPs with enhanced protease resistance and the development of peptide‐based nanomaterials for biomedical applications.

Source: Advanced Science

DOI: 10.1002/advs.202508854