Enhancing Antimicrobial Peptides from Frog Skin: A Rational Approach

CROSIO, MATIAS

Biomolecules

MDPI

Año: 2025 vol. 15

2218-273X

ntimicrobial resistance is a global health threat, which has been worsened by the slow development of new antibiotics. The rational design of natural-derived antimicrobial peptides (AMPs) offers a promising alternative for enhancing the efficacy of AMPs and accelerating drug discovery. This paper describes the rational design of improved peptide derivatives starting from hylin-Pul3, a peptide previously isolated from the frog Boana pulchella, by optimizing its hydrophobicity, cationicity, and amphipathicity. In silico screening identified six promising candidates: dHP3-31, dHP3-50, dHP3-50.137, dHP3-50.190, dHP3-84, and dHP3-84.39. These derivatives exhibited enhanced activity against Gram-negative bacteria, emphasizing the role of cationicity and the strategic arginine incorporation. Hemolytic assays revealed the derivatives? improved selectivity, particularly for the derivatives with ?imperfect amphipathicity?. In fibroblast assays, dHP3-84 was well-tolerated, while dHP3-84.39 promo