Host Defence Peptides from the Skin Glands of Australian Amphibians. Caerulein Neuropeptides and Antimicrobial, Anticancer, and nNOS Inhibiting Citropins from the Glandular Frog Litoria subglandulosa

Abstract

The host defence peptides from the skin secretions of the Australian Glandular Frog (Litoria subglandulosa) are similar to those of the closely related species Litoria citropa. Both species produce several potent caerulein neuropeptides and antimicrobial- and anticancer-active citropin peptides. The major neuropeptides from Litoria subglandulosa are caerulein 1.1 [pGlu Gln Asp Tyr(SO3) Thr Gly Trp Met Asp Phe–NH2], caerulein 1.2 [pGlu Gln Asp Tyr(SO3) Thr Gly Trp Phe Asp Phe–NH2], and caerulein 2.1 [pGlu Gln Asp Tyr(SO3) Thr Gly Ala His Met Phe–NH2], all of which are smooth muscle active. The major peptide, citropin 1.2 [Gly Leu Phe Asp Ile Ile Lys Lys Val Ala Ser Val Val Gly Gly Leu–NH2], is a wide-spectrum antibiotic and anticancer agent at the micromolar concentration. Citropin 1.2 also inhibits the formation of nitric oxide by the enzyme neuronal nitric oxide synthase (nNOS) at the micromolar concentration. Another peptide, citropin 2.2 [Gly Leu Ile Ser Ile Gly Lys Ala Leu Gly Gly Leu Ile Val Asp Val Leu Lys Pro Lys Ser–OH], also inhibits nNOS.