Gut-hormone fragment for digestion research (Gastrin-34 [1-10])
A short lab-made piece of the gut hormone gastrin, used in research to study how the stomach and gut signal fullness; not a drug, 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
Gastrin-34 [1-10] is a synthetic nine-residue peptide corresponding to the first nine amino acids at the N-terminal end of gastrin-34 (also called "big gastrin"), one of the naturally occurring forms of the gut hormone gastrin. Unlike the full gastrin-34 molecule, this short fragment does not carry the C-terminal sequence that drives classical gastrin biology. It is used in research settings to study how different parts of the gastrin precursor interact with cholecystokinin receptors — particularly the cholecystokinin A receptor (CCKAR, also called CCK1R).
History
Gastrin-34 was established as a distinct molecular form of gastrin in the early 1980s, when Boel and colleagues (1983) reported the molecular cloning of human gastrin cDNA from a gastrin-producing pancreatic tumor (gastrinoma), revealing a 101-residue preprogastrin precursor. Their sequence data showed that the precursor encodes big gastrin (gastrin-34) as one post-translational product, and provided evidence that the gastrin gene evolved through gene duplication (Boel and colleagues, 1983). The N-terminal region of gastrin-34 — which contains the sequence making up this fragment — had already been the subject of immunochemical mapping studies by that time, with antisera raised against synthetic N-terminal peptides used to localize distinct antigenic determinants within the first 1–15 residues of big gastrin.
What it does
Gastrin-34 [1-10] encompasses the unique N-terminal segment that distinguishes big gastrin (34 residues) from its shorter relative, little gastrin (gastrin-17). The full gastrin-34 molecule acts principally via the cholecystokinin B receptor (CCK2R / CCKBR) to stimulate gastric acid secretion from parietal cells, promote growth of the gastric mucosa, and release histamine from enterochromaffin-like cells (Zeng and colleagues, 2020). However, the bioactive core of gastrin is confined to the C-terminal pentapeptide sequence — the N-terminal portion of gastrin-34 does not itself mediate these classical actions.
This N-terminal fragment is used experimentally to probe the ligand-interaction surface of the cholecystokinin A receptor (CCKAR). CCK1R and CCK2R are structurally related class A GPCRs that are approximately 50% identical overall, with the greatest divergence in the binding-pocket regions that determine their very different selectivity profiles (Miller and colleagues, 2008). CCK1R strongly prefers cholecystokinin, which carries a sulfated tyrosine in its extended C-terminal heptapeptide; gastrin-derived fragments lacking this sulfated extension are low-affinity ligands at CCK1R. Fragments such as Gastrin-34 [1-10] can be used to examine which portions of the receptor's extracellular and transmembrane surfaces are engaged by different structural features of the gastrin/CCK ligand family.
Evidence
- Human: No human clinical data for this fragment. It is a research tool, not a therapeutic compound.
- Animal: Not reported for this fragment specifically. Pharmacological studies of the gastrin/CCK receptor family in rat and other models have characterized the structural requirements for CCK1R versus CCK2R activation (Miller and colleagues, 2008).
- In vitro: Used in receptor-binding and competition studies to map ligand–receptor contacts at CCKAR. The broader gastrin family literature has characterized that the C-terminal tetrapeptide amide is the minimal CCK2R-active unit, while CCK1R requires the full sulfated heptapeptide (Miller and colleagues, 2008).
Known effects
- CCKAR ligand interaction probe — Research tool; used to characterize binding-pocket interactions at the cholecystokinin A receptor.
- No endocrine agonist activity — The N-terminal 1–10 fragment of gastrin-34 lacks the C-terminal pharmacophore required for classical gastrin signaling at CCK2R (Zeng and colleagues, 2020).
Mechanism
Gastrin bioactivity is encoded entirely in its C-terminal region. All biologically active gastrin and CCK peptides share an amidated C-terminal pentapeptide motif (Gly-Trp-Met-Asp-Phe-NH₂) that is the minimal pharmacophoric unit for CCK2R activation (Zeng and colleagues, 2020). The CCK2R requires only this C-terminal tetrapeptide amide for high-affinity binding and signaling; it couples via phospholipase C (PLC), generating diacylglycerol and inositol trisphosphate, leading to protein kinase C activation and downstream proliferative and secretory responses (Zeng and colleagues, 2020). The N-terminal extension present in gastrin-34 — which this fragment represents — does not contact the CCK2R binding pocket in a way that contributes to activation. Its primary pharmacological contribution to the intact G-34 molecule is to extend plasma half-life, from roughly 7 minutes for gastrin-17 to approximately 38 minutes for gastrin-34.
The CCK1R (CCKAR) is structurally related but differs in ligand selectivity: it requires the carboxyl-terminal heptapeptide amide including a sulfated tyrosine found in CCK peptides, making gastrin a low-affinity, weakly potent agonist at this receptor — roughly 500- to 1,000-fold less potent than CCK (Miller and colleagues, 2008). Gastrin-34 [1-10], as the N-terminal fragment of big gastrin, is applied in binding studies to dissect which contacts along the CCKAR extracellular surface are engaged by different portions of gastrin-family ligands.
Open questions
- No specific receptor has been identified for N-terminal progastrin processing fragments; whether short N-terminal gastrin peptides engage any distinct receptor or binding site remains unresolved.
- The precise structural determinants within the N-terminal 1–10 region of gastrin-34 that distinguish CCK1R from CCK2R engagement have not been fully mapped with this isolated fragment.
- Proteolytic stability and plasma half-life of the isolated Gastrin-34 [1-10] nonapeptide have not been reported.
Related peptides
- Gastrin signaling and receptor biology are reviewed in the context of the broader CCK/gastrin family; see also related cards for the full gastrin forms and CCK receptor ligands on this platform.
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.
Can this short peptide really bind and activate the CCKAR receptor, or is the computer model giving a false positive?
If the docking score is a false positive, researchers could avoid wasting time testing this fragment as a CCKAR drug lead. It would also flag a potential flaw in how structure-prediction tools score short peptides against large receptors.
Does the absence of the natural protective cap at one end of this fragment change its shape enough to produce misleading results?
If the cap matters for shape, clinical tests that use this fragment to measure gastrin levels in blood could be systematically inaccurate, affecting diagnosis of gastrin-producing tumors (gastrinomas) in patients.
Does this fragment actually bind to the gastrin-type receptor rather than the CCK-type receptor it is listed under?
If the fragment has any preference for the gastrin receptor (CCK2R) over the CCK receptor (CCK1R), decades of experiments using it as a CCK1R probe would need reinterpretation, potentially changing our understanding of how big gastrin signals differently from little gastrin.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9647589921951294 | boltz-2 |
| ranking score | 0.8069562911987305 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.643 | 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{pep10615,
sequence = {LGPQGPPHL},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}