Dermorphin

Dermorphin

Dermorphin is a naturally occurring heptapeptide and an exceptionally potent, highly selective agonist of the μ‑opioid receptor (MOR), the principal receptor subtype mediating classical opioid analgesia and many neuromodulatory effects. Isolated from the skin secretions of South American Phyllomedusa frogs, Dermorphin has the primary structure H‑Tyr‑D‑Ala‑Phe‑Gly‑Tyr‑Pro‑Ser‑NH₂. The presence of a D‑alanine residue at position 2—a strikingly rare feature among natural peptides—substantially enhances resistance to enzymatic degradation and markedly increases MOR binding affinity and in vivo stability.

Owing to its unusually high potency, strong MOR selectivity, and prolonged receptor engagement, Dermorphin is widely used as a model ligand in opioid research. It enables detailed investigation of μ‑opioid receptor pharmacology, nociceptive pathway modulation, and G‑protein–coupled receptor (GPCR) signaling.

Dermorphin from Montreal Peptides Canada is supplied as a high‑purity, research‑grade lyophilized peptide. It is intended exclusively for laboratory and scientific research and is not approved for human or veterinary administration, diagnosis, treatment, or consumption.

Dermorphin Overview

Dermorphin’s distinct pharmacological profile arises from the combination of its peptide backbone and unique stereochemical configuration:

• Sequence: H‑Tyr‑D‑Ala‑Phe‑Gly‑Tyr‑Pro‑Ser‑NH₂
• Unique feature: D‑Ala at position 2 (D‑amino acid in a naturally occurring peptide)
• Key outcomes: High MOR affinity, enhanced metabolic stability, and extended duration of action

Compared with classical opioid ligands (e.g., morphine, β‑endorphin), Dermorphin:

• Demonstrates significantly higher potency at μ‑opioid receptors
• Exhibits marked selectivity for MOR over κ‑ and δ‑opioid receptor subtypes
• Displays slow off‑rate kinetics, resulting in sustained receptor occupancy

Upon binding MOR, Dermorphin engages canonical opioid signaling:

• Inhibition of adenylate cyclase and decreased cAMP levels
• Modulation of ion channels (reduced Ca²⁺ influx, increased K⁺ conductance)
• Suppression of neurotransmitter release at presynaptic terminals

These effects produce robust antinociceptive and sedative responses in experimental systems and make Dermorphin a valuable reference compound for dissecting MOR‑mediated signaling and GPCR function.

Dermorphin Structure

Chemical Makeup

• Molecular Formula: C₄₀H₅₀N₈O₁₀
• Molecular Weight: 802.88 Da
• Observed Mass (Batch #2025034): 802.9 Da
• Purity: 99.09% (confirmed by HPLC and LCMS)
• Form: Lyophilized peptide powder
• Analytical Methods:
• Reverse‑phase HPLC (UV detection at 214 nm)
• LCMS (ESI⁺ mode), calibrated against a synthetic Dermorphin reference standard
• Appearance: White to off‑white crystalline powder

Dermorphin Research

μ‑Opioid Receptor Binding and Selectivity

Dermorphin is one of the most potent and selective natural ligands for the μ‑opioid receptor:

• High‑affinity MOR agonist: Radioligand binding and competition assays indicate low‑nanomolar to subnanomolar affinity for MOR.
• Subtype selectivity: Activity at κ‑ and δ‑opioid receptor subtypes is comparatively low, allowing focused interrogation of μ‑mediated effects.
• Slow dissociation: Prolonged receptor occupancy provides a stable platform for analyzing MOR signaling, internalization, and regulatory mechanisms over time.

These properties make Dermorphin an ideal probe for:

• Mapping MOR binding domains and critical ligand–receptor interactions
• Comparing binding kinetics and efficacy among opioid agonists and peptide analogues
• Investigating the structural basis for μ‑opioid selectivity versus κ‑ and δ‑receptor engagement

Analgesic Mechanisms

Dermorphin is widely used in experimental pain models as a reference μ‑opioid agonist:

• Potent, long‑lasting analgesia: In animal studies, Dermorphin frequently exhibits stronger and more sustained antinociceptive effects than morphine.
• Enhanced stability in vivo: The D‑Ala residue protects against rapid proteolysis, extending the peptide’s duration of action and enabling analysis of prolonged MOR activation.
• Tolerance and adaptation studies: Its long‑lasting activity makes it useful for exploring the development of tolerance, receptor desensitization, and adaptations within nociceptive pathways during repeated or chronic MOR stimulation.

These attributes support research on both the therapeutic potential and the adaptive consequences of sustained μ‑opioid receptor activation.

Neurochemical and Behavioral Studies

Dermorphin has been extensively employed to elucidate μ‑opioid–mediated modulation of central nervous system function:

• Neurotransmission and synaptic plasticity: Dermorphin influences the release of key neurotransmitters and neuromodulators (e.g., glutamate, GABA, monoamines), altering synaptic strength and transmission within pain and reward circuits.
• Neuronal excitability: Via MOR‑mediated ion‑channel modulation, Dermorphin can regulate firing patterns and excitability in spinal and supraspinal neurons involved in nociception, stress, and reinforcement.
• GPCR signaling dynamics: It provides a robust model for studying G‑protein versus β‑arrestin signaling, receptor desensitization, internalization, and long‑term neuroadaptive changes associated with repeated μ‑receptor activation.

These lines of investigation contribute to a more complete understanding of how μ‑opioid receptor signaling shapes cellular, circuit‑level, and behavioral outcomes relevant to analgesia, dependence, and opioid‑induced neuroplasticity.

Article Author

This literature review is presented in recognition of the foundational work of Dr. Vittorio Erspamer, M.D., Ph.D. Dr. Erspamer was a renowned Italian pharmacologist and biochemist noted for discovering and characterizing numerous bioactive peptides from amphibian skin, including dermorphin, deltorphin, and bombesin. His meticulous isolation, structural elucidation, and pharmacological analysis of Dermorphin established it as a prototype natural μ‑opioid receptor agonist and significantly advanced the fields of neuropharmacology, peptide chemistry, and peptide‑based therapeutics.

Scientific Journal Author

The initial discovery and characterization of Dermorphin were achieved by Dr. Vittorio Erspamer and his collaborators P.C. Montecucchi, R. De Castiglione, S. Piani, L. Gozzini, and M. Broccardo. Their pioneering studies:

• Identified Dermorphin as a novel peptide with potent opiate‑like activity from amphibian skin
• Determined its primary structure and distinctive inclusion of D‑Ala
• Demonstrated its high potency and selectivity as a μ‑opioid receptor agonist in both central and peripheral systems

Subsequent investigations by researchers such as L. Negri, G. Lazzeri, C.H. Li, and D. Chung expanded on this foundation by exploring receptor‑binding profiles, analog design, and detailed structure–activity relationships.

This acknowledgment is provided solely to recognize the scientific contributions of Dr. Erspamer and his colleagues. It does not imply endorsement, affiliation, or sponsorship between Montreal Peptides Canada and any of the researchers or institutions mentioned.

Reference Citations

1. Montecucchi PC, De Castiglione R, Piani S, Gozzini L, Erspamer V. A novel amphibian skin peptide with potent opiate-like activity. Nature. 1981;292(5826):608–610. https://pubmed.ncbi.nlm.nih.gov/7198101/
2. Erspamer V, et al. Dermorphin: a potent natural analgesic peptide from amphibian skin. Eur J Pharmacol. 1982;78(3):337–342. https://pubmed.ncbi.nlm.nih.gov/6288442/
3. Negri L, et al. Pharmacological activity and receptor binding of dermorphin analogs. Peptides. 1985;6(Suppl 3):87–91. https://pubmed.ncbi.nlm.nih.gov/2413894/
4. Broccardo M, et al. Central and peripheral activity of dermorphin in animal models. Br J Pharmacol. 1981;73(3):625–631. https://pubmed.ncbi.nlm.nih.gov/6264952/
5. Li CH, Chung D. Synthetic peptides related to dermorphin: receptor binding and bioactivity. Biochemistry. 1983;22(8):1923–1928. https://pubmed.ncbi.nlm.nih.gov/6300120/
6. Lazzeri G, Negri L, et al. Receptor selectivity of dermorphin analogues. Eur J Pharmacol. 1985;110(3):357–363. https://pubmed.ncbi.nlm.nih.gov/2988703/
7. Stefano GB, et al. Opiate receptor activity in invertebrate and vertebrate systems: insights from dermorphin analogues. Proc Natl Acad Sci U S A. 1989;86(22):8977–8981. https://pubmed.ncbi.nlm.nih.gov/2573076/
8. Williams JT, Christie MJ, Manzoni O. Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev. 2001;81(1):299–343. https://pubmed.ncbi.nlm.nih.gov/11152759/
9. DrugBank Online. Dermorphin. https://go.drugbank.com/drugs/DB13355
10. National Center for Biotechnology Information. Dermorphin compound summary. PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/Dermorphin

HPLC/MS

HPLC

Dermorphin purity is analyzed by reverse‑phase high‑performance liquid chromatography (RP‑HPLC) with UV detection at 214 nm. The chromatogram displays a single predominant peak corresponding to Dermorphin, with total impurities below 1%, in agreement with the reported purity of 99.09%. This level of chromatographic purity is appropriate for high‑precision laboratory and in vitro applications.

MS

Mass spectrometric characterization (LCMS, ESI⁺ mode) confirms the expected molecular ion for Dermorphin, with an observed mass of approximately 802.9 Da. This value is in excellent agreement with the theoretical molecular weight of 802.88 Da. No major additional signals consistent with truncated sequences, isomers, or significant degradation products are detected within the sensitivity of the method.

STORAGE

Storage Instructions

All peptides are manufactured using a lyophilization (freeze‑drying) process, which stabilizes them for shipping and short‑term handling (approximately 3–4 months). After reconstitution with bacteriostatic water:

• Store the peptide solution at ~4°C (39°F).
• Under these conditions, most peptide solutions remain stable for up to 30 days.

Lyophilization (cryodesiccation) involves freezing the peptide and applying low pressure so that water sublimates directly from ice to vapor, leaving a stable, dry peptide powder. This lyophilized form is typically suitable for short‑term room‑temperature storage prior to reconstitution.

For long‑term storage (months to years):

• Store lyophilized peptides at −80°C (−112°F).
• Protect from light and moisture to maintain structural integrity and bioactivity.

Upon arrival, peptides should be transferred promptly to cold, dark storage. For short‑term use (days to a few months), refrigeration below 4°C (39°F) is generally adequate; lyophilized peptides usually remain stable at room temperature for several weeks.

Best Practices For Storing Peptides

To maximize stability and experimental reliability:

• Keep peptides cool and protected from light as soon as they are received.
• Use refrigeration (≤4°C / 39°F) for short‑ to medium‑term storage.
• Store at −80°C (−112°F) for long‑term preservation.
• Avoid frost‑free freezers, which undergo temperature cycling during defrost.
• Minimize freeze‑thaw cycles, as repeated thermal stress accelerates degradation.

Even for relatively stable sequences, these practices help maintain purity, potency, and reproducibility.

Preventing Oxidation and Moisture Contamination

Exposure to air and moisture can promote peptide degradation:

• Allow frozen vials to warm to room temperature before opening to prevent condensation.
• Keep vials tightly sealed and reseal immediately after withdrawing material.
• When feasible, store remaining peptide under a dry, inert gas (e.g., nitrogen or argon) to reduce oxidative reactions.

Peptides containing cysteine (C), methionine (M), or tryptophan (W) residues are especially prone to oxidation and should be handled with additional care. To reduce repeated exposure to air and temperature changes, divide bulk peptide into small aliquots appropriate for single or limited experimental uses.

Storing Peptides In Solution

Peptide solutions are less stable than lyophilized powders and more susceptible to hydrolysis and microbial contamination:

• Prepare solutions in sterile buffers with a pH of approximately 5–6 when possible.
• Make small aliquots to avoid repeated freeze‑thaw cycles.
• At 4°C (39°F), most peptide solutions remain stable for up to 30 days.
• For more labile peptides, store solutions frozen when not in immediate use.

Whenever practical, maintain peptides in lyophilized form and reconstitute fresh solutions shortly before experiments.

Peptide Storage Containers

Appropriate containers further support peptide stability:

• Use clean, chemically inert vials sized to minimize headspace.
• Glass vials provide excellent chemical resistance and visual clarity.
• Plastic vials (polystyrene or polypropylene) are also suitable:
• Polystyrene: clear and easy to inspect, but less chemically resistant
• Polypropylene: more chemically robust, typically translucent

Peptides are often shipped in plastic to reduce breakage risk. Transfers between glass and plastic vials are acceptable if performed carefully under clean conditions to avoid contamination.

Peptide Storage Guidelines: General Tips

To preserve peptide quality over time:

• Store in a cold, dry, and dark environment.
• Avoid repeated freeze‑thaw cycles.
• Minimize exposure to air to limit oxidation.
• Protect from prolonged or intense light.
• Prefer lyophilized storage for long‑term keeping; avoid extended storage in solution.
• Aliquot peptides to match experimental needs and reduce repeated handling and environmental exposure.