Introduction: Anti-microbial resistance (AMR) represents a significant danger to public health, particularly regarding diabetic foot ulcers (DFUs), where traditional antibiotics frequently fail to combat biofilm-producing pathogens. The objective of this study was to analyze the multifunctional aspects of a new wasp kinin derivative, PMM4 (H-Lys-Arg-Arg-Pro-Gly-Phe- Thr-Pro-Phe-Arg-OH; 1260.8 Da), which has been developed to improve antimicrobial effectiveness while maintaining low levels of cytotoxicity and offering anti-oxidant, anti-inflammatory, and anti-hyperglycaemic advantages. Methods: PMM4 was specifically synthesized and tested for its antimicrobial properties, α- amylase inhibition, anti-oxidant activity (DPPH), and anti-inflammatory effects (albumin denaturation). Cytolytic, hemolytic, and MTT assays were employed to evaluate cytocompatibility using erythrocytes and Vero cells, while zebrafish embryo toxicity was assessed in accordance with OECD TG 236 guidelines. Results: PMM4 displayed extensive bacteriolytic effectiveness with MIC values ranging from 5 to 10 μg/mL and less than 3% hemolysis at a concentration of 30 μg/mL. The peptide showed strong DPPH scavenging capability (IC₅₀ = 70.8 μg/mL), inhibited α-amylase (IC₅₀ = 73.7 μg/mL), and exhibited anti-denaturation effects (IC₅₀ = 60.8 μg/mL). Zebrafish embryos demonstrated over 95% survival at concentrations of 36 μg/mL or less, with an LC₅₀ exceeding 60 μg/mL, and Verocell viability remained at or above 85% up to 625 μg/mL, indicating low toxicity. Discussion: The activity profile of PMM4 indicates a dual action that involves disruption of membranes and potentially (p)ppGpp binding, along with metabolic and host-modulatory advantages that are essential for healing diabetic wounds. Conclusion: PMM4 stands out as a promising multifunctional therapeutic peptide that possesses wide-ranging antimicrobial, anti-oxidant, and anti-inflammatory properties, along with excellent biocompatibility, justifying further preclinical exploration for managing infected diabetic wounds.
Moses et al. (Tue,) studied this question.