Dynorphin A: natural opioid pain and stress signal (porcine form)
A natural opioid peptide the body makes from a larger precursor; activates opioid receptors to modulate pain and stress responses. Used as a lab research tool.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Dynorphin A (1-17) is a 17-amino-acid opioid peptide that the body makes naturally — it is the cleavage product of a larger precursor protein called prodynorphin (specifically residues 209–225 of the porcine prodynorphin sequence). It was first isolated from pig pituitary glands and identified as an extraordinarily potent opioid (Goldstein 1981). The stored sequence here, YGGFLRRIRPKLKWDNQ, is the porcine form; the first five residues (YGGFL) are the same Leu-enkephalin "opioid motif" found at the start of many endogenous opioid peptides, and the C-terminal extension is what distinguishes dynorphin from the shorter enkephalins.
History
Dynorphin was named for its dynamic potency in opioid bioassays. Goldstein and colleagues determined the complete primary structure of the heptadecapeptide from porcine pituitary in 1981, reporting it as Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln and showing that the synthetic peptide of this sequence behaved identically to the natural material in the guinea pig ileum myenteric plexus–longitudinal muscle bioassay (Goldstein 1981). The same paper established that the first 13 residues account for the potency, a finding that has shaped subsequent structure–activity work on dynorphin fragments.
What it does
Dynorphin A (1-17) acts on the opioid receptor family — a set of G-protein-coupled receptors that endogenous opioid peptides use to dampen pain signaling, modulate reward and motivation, and regulate functions such as gastrointestinal motility (Sobczak 2014). Dynorphins are best known as endogenous ligands of the kappa-opioid receptor system, and the pharmacology of kappa-opioid receptor–related ligands has been studied extensively in non-human primates (Ko 2020). On this platform the card's annotated target is the mu-opioid receptor (oprm1), reflecting that dynorphin A also interacts with the broader mu-opioid receptor family whose biology has been reviewed in depth (Pasternak 2013).
Mechanism
Dynorphin A (1-17) belongs to the prodynorphin-derived family of endogenous opioid peptides, alongside dynorphin B and the related "big dynorphin" — all of which share the N-terminal YGGFL "message" sequence with the enkephalins and differ in their C-terminal "address" extensions (Clynen 2014). The Tyr-Gly-Gly-Phe motif is required for opioid receptor engagement; the basic residues that follow (Arg-Arg, Arg, Lys, Lys) form a positively charged C-terminal "address" that biases the peptide toward the kappa-opioid receptor relative to the shorter enkephalins. Goldstein (1981) showed that truncating dynorphin to its first 13 residues preserves potency in the guinea pig ileum assay, indicating that the terminal Trp-Asp-Asn-Gln tail is not essential for the bioassay activity measured there.
The mu-opioid receptor (MOR) — the target annotated on this card — and the closely related nociceptin/orphanin FQ receptor show divergent, cell-type-specific signaling within the mesocorticolimbic reward circuitry, with MOR activation enhancing reward processing and reinforcement by facilitating dopamine transmission in the ventral tegmental area and nucleus accumbens (Allichon 2026).
Evidence
- Human: No registered clinical trials for dynorphin A (1-17) on ClinicalTrials.gov; the peptide is studied as an endogenous neuromodulator and pharmacological tool rather than as a clinical drug candidate.
- Animal: Characterized in vivo in the guinea pig ileum bioassay at the time of structure elucidation (Goldstein 1981); kappa-opioid receptor pharmacology of related ligands extensively studied in non-human primates (Ko 2020).
- In vitro: Engagement of opioid receptors in tissue preparations is documented; comparative opioid binding methodology in rat brain has been established for related opioid peptides such as dermorphin (Amiche 1990).
Known effects
- Endogenous opioid signaling — Established. Acts on the opioid receptor family that mediates analgesia, reward modulation, and autonomic regulation (Pasternak 2013; Ko 2020).
- Gastrointestinal motility modulation — Mechanistic and tissue-level evidence. Opioid receptors and their endogenous ligands modulate motility, secretion, and visceral sensation in the GI tract (Sobczak 2014).
- Neuropeptide target for anticonvulsant research — Mechanistic. Dynorphin-A is listed among the prodynorphin-derived neuropeptides reviewed as targets for anticonvulsant drug development (Clynen 2014).
- Mesocorticolimbic reward signaling (via mu-opioid receptor) — Mechanistic. MOR and NOPR exhibit cell-type-specific actions in the prefrontal cortex, ventral tegmental area, and nucleus accumbens (Allichon 2026).
Regulatory status
- US (FDA): Not an approved drug. Dynorphin A (1-17) is studied as an endogenous peptide and research tool.
- EU (EMA): Not an approved drug.
- WADA: Not separately listed; endogenous opioid peptide.
Related peptides
- Dermorphin — amphibian-skin opioid heptapeptide with a D-Ala residue; used as a selective mu-opioid receptor probe (Amiche 1990).
Other prodynorphin-derived peptides (dynorphin B, big dynorphin, α-neoendorphin) and the enkephalins share the N-terminal YGGF "opioid motif" and represent the broader endogenous opioid system around this card (Clynen 2014).
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does the rigid proline at position 10 act like a switch that separates two functional regions of dynorphin, letting the peptide choose between different pain receptors?
Understanding this hinge could let chemists design short dynorphin-inspired peptides that precisely target one receptor subtype over another, opening a path to more targeted painkillers or anti-addiction medicines with fewer side effects.
Could dynorphin A, already known as a pain signal, also directly kill bacteria through its positively charged amino acids?
If dynorphin A has antimicrobial properties, it could inspire peptide drugs that simultaneously reduce pain and fight infection at wound sites or in the gut, addressing two problems with one molecule and potentially reducing the need for separate antibiotic treatments.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7024305462837219 | boltz-2 |
| ranking score | 0.7648069262504578 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.100 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10704,
sequence = {YGGFLRRIRPKLKWDNQ},
target = {oprm1},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}