Phylloxin, a novel peptide antibiotic of the dermaseptin family of antimicrobial/opioid peptide precursors

A novel family of peptide precursors that have very similar N-terminal prep rosequences followed by markedly different C-terminal domains has been iden tified in the skin of hylid frogs belonging to the genus Phyllomedusinae. B iologically active peptides derived from the variable domains include the d ermaseptins, 28-34-residue peptides that have a broad-spectrum microbicidal activity, and dermorphin and the deltorphins, D-amino acid containing hept apeptides that are very potent agonists for the mu-opioid and delta-opioid receptors, respectively. This report describes the isolation, synthesis and cloning of phylloxin, a prototypical member of a novel family of antimicro bial peptides derived from the processing of a dermaseptin/dermorphin-like precursor. The structure of phylloxin (GWMSKIASGIGTFLSCIQQ amide) shows no homology to the dermaseptins, but bears some resemblance to the levitide-pr ecursor fragment and the xenopsin-precursor fragment, two antimicrobial pep tides isolated from the skin of an evolutionarily distant frog species, Xen opus laevis. Circular dichroism spectra of phylloxin in low polarity medium , which mimics the lipophilicity of the membrane of target microorganisms, indicated 60-70% alpha-helical conformation, and predictions of secondary s tructure suggested that the peptide can be configured as an amphipathic hel ix spanning residues 1-19. Phylloxin is an addition to the structurally and functionally diverse peptide families encoded by the rapidly evolving C-te rminal domains of the dermorphin/dermaseptin group of precursors.