Peptide HV2 (histidine-rich peptide)

Antibacterial peptides (APMs) are a new type of antibacterial substance. The relationshipbetween their structure and function remains indistinct; in particular, there is a lack of a definitiveand fixed template for designing new antimicrobial peptides. Previous studies have shown thatporcine Protegrin-1 (PG-1) exhibits considerable antimicrobial activity and cytotoxicity. In this study,to reduce cytotoxicity and increase cell selectivity, we designed histidine-rich peptides based onthe sequence template RR(XY)2X-D-PGX(YX)2RR-NH2, where X represents I,W, V, and F. The resultsshowed that the peptides form more -hairpin structures in a lipid-rich environment that mimicscell membranes. Among them, the antimicrobial peptide HV2 showed strong antibacterial activityagainst Gram-negative strains and almost no toxicity to normal cells. The results of our analysis of itsantibacterial mechanism showed that peptide HV2 acts on the bacterial cell membrane to increase itspermeability, resulting in cell membrane disruption and death. Furthermore, peptide HV2 inhibitedbacterial movement in a concentration-dependent manner and had a more robust anti-inflammatoryeffect by inhibiting the production of TNF-alpha. In summary, peptide HV2 exhibits high bactericidalactivity and cell selectivity, making it a promising candidate for future use as an antibiotic.