A family of acyclic brevinin-1 peptides from the skin of the Ryukyu brown frog Rana okinavana

The 24 amino-acid residue antimicrobial peptide, brevinin-1 is synthesized in the skins of a wide range of species of Eurasian and North American frogs belonging to the genus Rana. All previously characterized brevinin-1 peptides contain the cyclic heptapeptide domain Cys ¹⁸-(Xaa) ₄-Lys-Cys ²⁴ at the COOH-terminus of the molecule. Four structurally related peptides were isolated from an extract of the skin of the Ryukyu brown frog Rana okinavana. The amino acid sequences of the peptides [Phe-(Xaa) ₄-Ile-(Xaa) ₂-Leu-Ala-Lys-Gly-Leu-Pro-Ser-Leu- Ile-Xaa-Leu-Xaa-Lys-Lys·NH ₂] identified them as members of the brevinin-1 family that lacked the COOH-terminal cyclic domain but contained a C-terminally α-amidated residue. It is suggested, as one possibility, that the Cys ¹⁸ in the brevinin-1 consensus sequence has been deleted and the Cys ²⁴ residue has mutated to a glycine that acts as substrate for peptidyl-glycine α-amidating monooxygenase. The peptides potently inhibited the growth of Escherichia coli and Staphylococcus aureus confirming that a cyclic domain is not necessary for antimicrobial activity. A fifth peptide (SFLNFFKGAA ¹⁰KNLLAAGLDK ²⁰LKCKISGTQC ³⁰), that also displayed broad-spectrum antimicrobial activity, was isolated from the skin extract and showed structural similarity with members of the ranatuerin-2 family previously isolated from the skin of North American ranid frogs.