Dermorphin

Dermorphin is a natural heptapeptide first isolated from the skin of South American frogs belonging to the genus Phyllomedusa, including Phyllomedusa sauvagei (Sauvage's leaf frog), Phyllomedusa hypochondrialis, and Phasmahyla jandaia. It is a potent and selective μ-opioid receptor (MOR) agonist with an amino acid sequence of Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂. Dermorphin is unique among vertebrate peptides in containing a D-amino acid residue (D-Ala at position 2), a structural feature that is critical for its biological activity and resistance to enzymatic degradation. The peptide exhibits opiate-like activity approximately 30–40 times more potent than morphine and has been extensively studied as a research tool for investigating opioid receptor signaling, analgesia, and neuropathic pain mechanisms.

Dermorphin exerts its effects by selectively binding to and activating the μ-opioid receptor (MOR), a G protein-coupled receptor (GPCR) expressed in the central and peripheral nervous systems. The presence of the D-Ala² residue is essential for high-affinity receptor binding and pharmacological activity. Upon receptor activation, dermorphin triggers intracellular signaling cascades involving G protein-mediated inhibition of adenylate cyclase, decreased cyclic AMP production, and modulation of ion channel activity, ultimately producing potent antinociceptive (analgesic) effects. Receptor internalization has been shown to contribute to dermorphin-mediated antinociception. Unlike many other opioid peptides, dermorphin demonstrates high selectivity for μ-opioid receptors with minimal interaction at δ- and κ-opioid receptors.

• Pain and Analgesia Research: Investigated as a potent analgesic agent in preclinical models of nociceptive and neuropathic pain.
• Opioid Receptor Studies: Employed as a selective μ-opioid receptor agonist to study receptor binding, signaling pathways, internalization, and structure-activity relationships.
• Neuropharmacology: Utilized to investigate opioid-mediated effects on locomotor activity, gastrointestinal transit, and central nervous system function.
• Peptide Analog Development: Used as a lead compound for the design and synthesis of novel non-narcotic analgesic peptides with improved pharmacokinetic profiles.
• Drug Development: Studied in the development of comprehensive quality control approaches for synthetic opioid peptides.

CAS Number: 77614-16-5
PubChem CID: 5485199
Molecular Formula: C₄₀H₅₀N₈O₁₀
Molecular Weight: 802.87 g/mol
Sequence: Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂ (YaFGYPS-NH₂, where a = D-Ala)
Purity: ≥ 99%
Form: Lyophilized powder
Storage: Store at ≤ -20°C in a cool, dry place, protected from light and moisture
Solubility: Soluble in sterile water and DMSO; prepare working solutions per laboratory protocol