Natural opioid brain peptide (Dynorphin A 1-13)
A naturally occurring fragment of dynorphin, one of the brain's own opioid chemicals; used only as a lab research tool to study how the body's pain-relief system works.
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 (1-13) is a 13-amino-acid fragment of dynorphin A, an endogenous opioid peptide first isolated from pig pituitary. It corresponds to the N-terminal stretch of the full dynorphin A sequence and contains, embedded at its own N-terminus, the well-known opioid pentapeptide Leu-enkephalin (the first five residues, YGGFL). The fragment was singled out because, despite being shorter than the parent peptide, it retains essentially all of dynorphin's opioid activity, which made it a convenient tool for probing how the body's own opioids work.
History
Dynorphin was characterized by Avram Goldstein's group at Stanford, and the truncated 1-13 form was reported in 1979 as "an extraordinarily potent opioid peptide" derived from the N-terminal sequence of a novel porcine pituitary endorphin (Goldstein 1979). In the guinea-pig ileum longitudinal-muscle preparation it was about 700 times more potent than [Leu]enkephalin, and in the mouse vas deferens it was roughly 3 times more potent than [Leu]enkephalin — figures that placed it well outside the range of any opioid peptide known at the time (Goldstein 1979). The same study noted that naloxone fully blocked its effect in the ileum but with about 1/13 the apparent affinity it shows against [Leu]enkephalin or normorphine, an early hint that dynorphin engages opioid receptors differently than enkephalins do.
The years following its discovery reshaped how the opioid receptor family itself was understood. Functional cloning of the delta opioid receptor (Evans 1992) opened the modern molecular era of opioid pharmacology, and subsequent reviews trace how concepts of mu, delta, and kappa opioid receptors evolved as endogenous peptides like dynorphin A were dissected (Pasternak 2013; Valentino 2018). Comparative work has since shown that this opioid system is deeply conserved across vertebrates — receptor and precursor orthologues have been mapped even in jawless fish such as the Pacific hagfish (Huang 2022) — and mass-spectrometric neuropeptidome surveys continue to recover dynorphin-family peptides, including dynorphin A fragments, from mammalian brain tissue (Petruzziello 2012).
What it does
Dynorphin A (1-13) is a potent opioid agonist. In classical isolated-tissue assays it depresses electrically evoked contractions far more strongly than the enkephalins do, and that effect is reversed by the opioid antagonist naloxone (Goldstein 1979). Because the parent dynorphin A is the prototypical endogenous ligand for the kappa opioid receptor, dynorphin A (1-13) is most often used to mimic dynorphin's actions in the brain and gut. Beyond pain pathways, dynorphin-family peptides are implicated in seizure control, mood regulation, and stress responses, and they are discussed as a target class for anticonvulsant drug development (Clynen 2014). One notable behavioural observation is that dynorphin A-(1-13) given to mice reversed memory impairment caused by the neuropeptide galanin, pointing to a role beyond analgesia in modulating learning and memory circuits (Kameyama 1994).
On this platform the card's stored target is the mu opioid receptor (OPRM1), because the embedded Leu-enkephalin motif at residues 1–5 (YGGFL) means dynorphin A (1-13) does engage mu receptors as well — Goldstein's original assays in the guinea-pig ileum and mouse vas deferens are mu/delta-sensitive preparations, and the naloxone-blockade pattern reported in that paper is consistent with classical opioid-receptor activation (Goldstein 1979). The wider kappa-selective biology of the parent dynorphin sits adjacent to this card rather than inside it.
Evidence
- Human: No human clinical trials of dynorphin A (1-13) are captured in this dossier. It is used as a research peptide, not as an approved drug.
- Animal: Reversal of galanin-induced memory impairment in mice after central administration (Kameyama 1994). Comparative pharmacology of kappa-opioid-related ligands, including dynorphin-family peptides, has been characterized in non-human primates (Ko 2020).
- In vitro / isolated tissue: ~700-fold higher potency than [Leu]enkephalin in guinea-pig ileum and ~3-fold higher potency in mouse vas deferens; naloxone-reversible; reduced apparent naloxone affinity compared with [Leu]enkephalin or normorphine (Goldstein 1979). Detection of dynorphin A and related preprodynorphin-derived peptides in mammalian neuropeptidome surveys (Petruzziello 2012).
Known effects
- Opioid receptor activation (mu and kappa) — Mechanistic / isolated-tissue evidence (Goldstein 1979; Pasternak 2013).
- Modulation of memory processes in rodents — Preclinical, single landmark study (Kameyama 1994).
- Discussed as anticonvulsant lead class — Mechanistic review of dynorphin-family peptides as candidate anticonvulsant targets (Clynen 2014).
Regulatory status
Dynorphin A (1-13) is not an approved drug in any jurisdiction captured in this dossier. It is used as a laboratory reagent for probing endogenous opioid signaling. No FDA, EMA, or WADA listings for dynorphin A (1-13) are present in the source set.
Related peptides
- Dermorphin — an amphibian-skin-derived opioid peptide with a D-Ala residue, historically used alongside dynorphin fragments to map opioid receptor pharmacology (Broccardo 1981).
- Leu-enkephalin (YGGFL) — the pentapeptide that constitutes the N-terminus of dynorphin A (1-13); the reference compound against which Goldstein measured dynorphin's potency (Goldstein 1979).
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 basic tail of dynorphin A steer it mainly to the kappa opioid receptor, the one linked to stress and dysphoria, rather than to the morphine receptor it is currently labeled as targeting?
If dynorphin primarily acts at the kappa receptor, all research using it as a mu-receptor tool would need reinterpretation, and drugs designed to block dynorphin's effects would be better aimed at kappa receptors, a current focus for treating depression and cocaine addiction.
Do the three positively charged residues in the middle of dynorphin's tail grip a negatively charged groove on the kappa receptor that is absent on the morphine receptor, explaining kappa selectivity?
If this motif is confirmed as the selectivity switch, it could be transplanted onto simpler opioid scaffolds to create targeted kappa receptor drugs for painful itching (a condition where kappa agonists already show promise) without the side effects of non-selective opioids.
Could activating the kappa opioid receptor at doses that mimic natural dynorphin levels reduce relapse triggered by stress, while staying below the threshold that causes the unpleasant psychological effects seen at higher doses?
If a safe therapeutic window exists, this could revive an entire class of anti-addiction compounds that were abandoned, potentially providing the first effective pharmacotherapy for stress-triggered cocaine or alcohol relapse, a major driver of failed recovery.
Could bridging two amino acids in dynorphin A to form a closed loop protect the peptide from the enzymes that quickly destroy it, making it last long enough to be used as a research or therapeutic agent?
A stable form of dynorphin would let researchers properly study KOR's role in chronic pain, stress, and addiction using sustained dosing regimens, and could serve as the starting point for a new class of KOR-targeting drugs for conditions that currently have no approved treatments.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8724116683006287 | boltz-2 |
| ranking score | 0.816545307636261 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.837 | 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{pep10702,
sequence = {YGGFLRRIRPKLK},
target = {oprm1},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}