Multifunctional host-defense peptides isolated from skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae)

Five host-defense peptides (figainin 2PL, hylin PL, raniseptin PL, plasticin PL, and peptide YL) were isolated from norepinephrine-stimulated skin secretions of the banana tree dwelling frog Boana platanera (Hylidae; Hylinae) collected in Trinidad. Raniseptin PL (GVFDTVKKIGKAVGKFALGVAKNYLNS.NH ₂) and figainin 2PL (FLGTVLKLGKAIAKTVVPMLTNAMQPKQ. NH ₂) showed potent and rapid bactericidal activity against a range of clinically relevant Gram-positive and Gram-negative ESKAPE ⁺ pathogens and Clostridioides difficile. The peptides also showed potent cytotoxic activity (LC ₅₀ values < 30 μM) against A549, MDA-MB-231 and HT29 human tumor-derived cell lines but appreciably lower hemolytic activity against mouse erythrocytes (LC ₅₀ = 262 ± 14 μM for raniseptin PL and 157 ± 16 μM for figainin 2PL). Hylin PL (FLGLIPALAGAIGNLIK.NH ₂) showed relatively weak activity against microorganisms but was more hemolytic. The glycine-leucine-rich peptide with structural similarity to the plasticins (GLLSTVGGLVGGLLNNLGL.NH ₂) and the non-cytotoxic peptide YL (YVPGVIESLL.NH ₂) lacked antimicrobial and cytotoxic activities. Hylin PL, raniseptinPL and peptide YL stimulated the rate of release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥100 nM. Peptide YL was the most effective (2.3-fold increase compared with basal rate at 1 μM concentration) and may represent a template for the design of a new class of incretin-based anti-diabetic drugs.