Gut-fullness receptor probe (DYGWDF)
A tiny synthetic peptide that weakly latches onto the gut receptor the body uses to signal fullness after a meal; used only 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
This is a short synthetic peptide (six amino acids: DYGWDF) catalogued in ChEMBL as compound CHEMBL407057 and tested for binding to the CCK-1 receptor (CCKAR) — the receptor that the gut hormone cholecystokinin uses to trigger satiety, gallbladder contraction, and pancreatic enzyme release. The reported affinity is weak: Ki ≈ 3,200 nM at CCKAR. The sequence is built from the same C-terminal pharmacophore as cholecystokinin's active octapeptide (DYMGWMDF, sulfated at Tyr in the native hormone), and it appears in the medicinal-chemistry literature on hybrid peptides designed to engage both CCK and opioid receptors. It is a research tool, not a therapeutic.
What it does
In binding assays, the peptide acts as a weak ligand at the CCK-1 receptor (Ki ≈ 3,200 nM, ChEMBL CHEMBL407057). It does not have a clinical use, no animal efficacy data is attached to this card, and no functional signaling profile (agonist vs. antagonist potency) is recorded in the dossier — only the receptor-binding affinity. The peptide is structurally related to the C-terminal recognition motif of CCK that classical medicinal-chemistry work has used as a scaffold for designing CCK-receptor ligands and bifunctional opioid/CCK peptides (Boteju 1996; Agnes 2006; Lee 2006).
Evidence
- Human: No human studies of this specific 6-mer.
- Animal: No in vivo studies of this specific 6-mer are attached to this card.
- In vitro: Receptor binding at CCKAR with Ki ≈ 3,200 nM (ChEMBL CHEMBL407057). The peptide sits in a broader medicinal-chemistry literature that explored the CCK C-terminal hexa-/octapeptide scaffold and used it to design ligands that hit both CCK and opioid receptors. Boteju (1996) used topographical constraints at the Trp residue of the CCK-26–33 analog SNF 9007 (Asp-Tyr-D-Phe-Gly-Trp-(N-Me)Nle-Asp-Phe-NH2) to map receptor requirements at CCK-B and δ-opioid receptors. Agnes (2006) developed bifunctional peptides exploiting overlapping pharmacophores at opioid and cholecystokinin receptors. Lee (2006) designed hydrazide-linked bifunctional peptides as δ/μ opioid agonists and CCK-1/CCK-2 antagonists.
Mechanism
The CCK-1 receptor (CCKAR; also called CCK-A) is the receptor that mediates cholecystokinin's peripheral effects — satiety signaling via vagal afferents, gallbladder contraction, and pancreatic enzyme secretion. Native cholecystokinin's minimum active sequence at CCK-1 is its sulfated C-terminal octapeptide (DYMGWMDF-NH2, sulfated at Tyr). The DYGWDF hexapeptide stored on this card maps onto the C-terminal recognition motif of that pharmacophore. The Ki ≈ 3,200 nM affinity is several orders of magnitude weaker than native CCK-8 at CCK-1R, consistent with a partial or truncated pharmacophore rather than a full agonist ligand. The structured metadata on this card records only the binding affinity; no functional (cAMP, IP3, calcium) data is included.
Related peptides
Other peptides built on the cholecystokinin C-terminal pharmacophore — cholecystokinin itself (CCK-8, CCK-33, CCK-58), the diagnostic agent sincalide (synthetic sulfated CCK-8), and bifunctional opioid/CCK analogs such as SNF 9007 — share the same recognition motif. They differ from this card's peptide in sequence length, the presence of tyrosyl sulfation (essential for full CCK-1R potency in the native hormone), and the resulting receptor affinity.
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 this peptide designed for the fullness receptor also bind the receptor that controls stomach acid?
If it does, the same scaffold could be developed into treatments touching both appetite and gastric disorders, or into more precisely selective drugs by tweaking which receptor it prefers.
Can this six-amino-acid peptide activate the fullness receptor without the chemical modification that nature normally requires?
If true, it could point toward simpler synthetic drugs that trigger satiety signals, potentially helping people manage appetite without needing complex hormone-mimicking chemistry.
Does this peptide gently activate the fullness receptor, or does it just sit there without doing anything?
If it gently activates the receptor, it could become the basis for appetite-reducing compounds that work with a natural ceiling, potentially causing fewer side effects than full hormone mimics.
Could constraining this peptide into a ring-like structure make it grip the fullness receptor more precisely and resist breakdown?
If so, researchers would gain a cleaner chemical probe to study hunger and digestion signaling, which could accelerate the development of drugs for obesity or pancreatic disorders.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| Ki | 3200 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.067 | 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{pep10313,
sequence = {DYGWDF},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}