Scientific Reference
Dermorphin
Evidence profile: Predominantly preclinical
Dermorphin is a seven-residue opioid peptide first found in the skin secretions of South American frogs of the genus Phyllomedusa. Its second residue is D-alanine. Ribosomes incorporate only L-amino acids, so this residue arises by conversion of an ordinary L-amino acid after the peptide chain is made; dermorphin was among the first natural peptides in which this was shown, which gives it a place in peptide biochemistry beyond opioid research. Work on it has been largely pharmacological, using receptor-binding assays, isolated tissue preparations and animal models. It and its synthetic analogues serve as reference ligands for one opioid receptor type. Human data are minimal.
Mechanism of Action
Dermorphin has been reported to bind the mu-opioid receptor with high selectivity over the delta and kappa types. The mu receptor is a G protein-coupled receptor linked to Gi/o proteins; its activation inhibits adenylyl cyclase, opens inwardly rectifying potassium channels and closes voltage-gated calcium channels, which lowers neuronal excitability and transmitter release. Structure–activity work has focused on the N-terminal Tyr-D-Ala sequence, which is shared with other amphibian opioid peptides such as the deltorphins, and on how the D-residue slows breakdown by peptidases compared with the all-L form. Much of the literature uses dermorphin analogues as tools for mapping mu-receptor pharmacology.
Molecular Information
- Type: Heptapeptide
- Length: 7 amino acids
- Molecular weight: 802.9 g/mol
- Molecular formula: C40H50N8O10
- CAS: 77614-16-5