Rational design and bioactivity evaluation of antimicrobial peptides from the skin secretion of the frog, Pachymedusa dacnicolor

This study focuses on two AMP families—cationic QUB peptides and Medusin peptides—and an unusual anionic peptide, PD37. The novel AMP QUB3189 was used to design six analogues, revealing that shortening peptides reduced antimicrobial activity but lowered haemolysis, while increased α-helicity improved potency at the cost of higher cytotoxicity.

Among them, QUB2578 showed strong broad-spectrum activity with minimal haemolysis. Medusin PD analogues modified with D-amino acids and non-natural residues improved activity, especially against Gram-negative bacteria, and reduced toxicity. In contrast, PD37, with a net charge of –2, had poor antimicrobial efficacy despite optimization but low toxicity.