Gut hormone fragment used to study digestion (Gastrin-34 [1-9])
A short piece of the stomach hormone gastrin that researchers use to study how the gut signals fullness and controls gallbladder activity. Used only as a lab research tool.
- Class
- Gastrin fragment (N-terminal nonapeptide)
- Status
- No approved therapeutic status identified
- Main caveat
- The compiled source provides identity and chemistry data only; no bioactivity, animal, or human evidence is present in this card.
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 [1-9] is a short peptide covering the first nine amino acid positions of big gastrin (gastrin-34), the 34-residue form of the gut hormone gastrin. Gastrin is a hormone released by specialised G-cells in the stomach and duodenum that stimulates gastric acid secretion and promotes growth of the stomach lining. Gastrin-34, sometimes called "big gastrin," is the dominant form circulating between meals. The [1-9] fragment represented here (sequence LGPQGPPH) spans the N-terminal arm of gastrin-34 that distinguishes it from the shorter gastrin-17 — a region that does not itself carry agonist activity but has been characterised as a research probe for studying gastrin processing, plasma clearance, and the structural biology of the gastrin/CCK hormone family (Boel and colleagues, 1983; Zeng and colleagues, 2020).
The stored sequence LGPQGPPH corresponds to positions 2–9 of gastrin-34. The intact gastrin-34 molecule carries a pyroglutamic acid (pGlu) cyclisation at its true N-terminus (position 1), a modification that protects the peptide against aminopeptidase degradation; this pGlu residue is not represented in the single-letter sequence shown here.
History
Gastrin was first proposed as a humoral stimulant of gastric acid secretion in 1905 by John S. Edkins, who showed that antral mucosal extracts could trigger acid output and named the active substance "gastrin." Decades of debate followed, in part because early preparations were contaminated with histamine. The hormone's existence on independent terms was firmed up by Simon Komarov in 1938, who isolated an active, histamine-free gastrin preparation.
Structural characterisation arrived in the early 1960s when Roderick Gregory and Hector Tracy purified gastrin from pig antral mucosa, determining the sequences of gastrin-17 and gastrin-34 and showing that biological potency is concentrated entirely in the shared C-terminal amidated tetrapeptide. In 1983, Boel and colleagues cloned human gastrin cDNA from a gastrinoma mRNA library and deduced the full 101-amino-acid preprogastrin sequence. A striking internal sequence homology within the coding region led them to conclude that the gastrin gene arose by gene duplication of an ancestral precursor (Boel and colleagues, 1983). This placed gastrin and CCK in the same peptide gene family, with their two cognate receptors — CCK1R (previously CCK-A) and CCK2R (previously CCK-B) — reflecting that shared evolutionary origin.
Subsequent biochemical work characterised N-terminal fragments of gastrin-34 as natural circulating byproducts of gastrin processing, leading to the development of radioimmunoassays targeting the N-terminal sequence of G34 to distinguish it immunochemically from G17 and its metabolites.
What it does
When gastrin-34 is cleaved by trypsin-like proteases within G-cells, the N-terminal half and gastrin-17 (the C-terminal half) are released together. Studies in isolated rat stomach show that this N-terminal fragment is stored and secreted concomitantly with gastrin-17 upon stimulation, though not in a strictly stoichiometric ratio (Akai, 1988). N-terminal progastrin fragments as a class circulate at concentrations roughly 30-fold higher than mature gastrin forms during fasting (Goetze and colleagues, 2017).
The [1-9] fragment itself does not contain the C-terminal tetrapeptide motif (Trp-Met-Asp-Phe-NH₂) that all known biologically active gastrin and CCK peptides require for receptor activation (Zeng and colleagues, 2020). Infusion of the larger gastrin-34 N-terminal fragment (positions 1–17) into healthy human volunteers at doses up to 1,000 pmol·kg⁻¹·h⁻¹ produced no stimulation of basal or gastrin-17-evoked gastric acid output (Pauwels and colleagues, 1984). The primary documented applications of these N-terminal fragments are immunochemical and pharmacokinetic: as reference standards and immunogens in radioimmunoassays that can discriminate intact G34 from G17 and other processing intermediates in plasma and tissue.
Evidence
- Human: Infusion of the N-terminal 1–17 fragment of gastrin-34 into five healthy volunteers demonstrated rapid plasma clearance (t½ approximately 2.4 minutes) and no effect on basal or gastrin-17-stimulated gastric acid secretion across a wide dose range (Pauwels and colleagues, 1984). A separate study found that infusion of the progastrin 1–35 fragment (which encompasses the [1-9] region) reduced gastrin-17-stimulated acid output by approximately 30% at high doses, an effect dependent on the first five residues of the sequence (Goetze and colleagues, 2017). No clinical trials are registered on ClinicalTrials.gov for this fragment.
- Animal: Co-existence and co-release of the gastrin-34 N-terminal fragment alongside gastrin-17 was demonstrated in an isolated rat stomach perfusion model using methacholine and porcine gastrin-releasing peptide stimulation (Akai, 1988).
- In vitro: N-terminal-specific antisera raised against gastrin-34 positions 1–12 have been used as reference tools in radioimmunoassay-based studies to track gastrin processing intermediates in cell and tissue models.
Mechanism
Gastrin exerts its classical hormonal effects — acid secretion from parietal cells, trophic action on gastric mucosa, and stimulation of enterochromaffin-like cells — through CCK2R (the gastrin/CCK-B receptor). CCK2R is activated equally by gastrin and CCK because both share the required C-terminal tetrapeptide amide, and it is the cognate receptor for gastrin signalling (Zeng and colleagues, 2020).
CCK1R (the CCK-A receptor, the platform target linked to this card) mediates gallbladder contraction, pancreatic enzyme secretion, intestinal motility, and vagal satiety signalling — the classic effects attributed to gut CCK. CCK1R requires a C-terminal heptapeptide that includes a sulfated tyrosine (present in CCK but not in gastrin) for high-affinity activation; as a result, gastrin binds CCK1R approximately 500- to 1,000-fold less potently than sulfated CCK (Miller and Gao, 2008; Zeng and colleagues, 2020). Structural studies of CCK1R bound to sulfated CCK-8 identified Arg197 in the second extracellular loop as the key residue that coordinates the sulfate group and confers this ligand selectivity (Liu and colleagues, 2021).
The [1-9] N-terminal fragment (LGPQGPPH) lacks both the C-terminal pharmacophore and the sulfated tyrosine, and therefore does not activate CCK1R or CCK2R in the canonical sense. No specific receptor has been identified for any gastrin N-terminal processing intermediate (Goetze and colleagues, 2017). The fragment's structural interest is as a probe for studying the processing and clearance of big gastrin, and as an antigen for immunoassays that distinguish G34 from G17 in biological samples.
Related peptides
- Gastrin-17 — The shorter, meal-stimulated active form of gastrin; the C-terminal product released alongside this N-terminal arm during gastrin-34 processing; carries the full active pharmacophore at CCK2R.
- Cholecystokinin (CCK-8, CCK-33) — Closest structural and functional relative; shares the C-terminal pentapeptide with gastrin but acts preferentially at CCK1R (via its sulfated tyrosine) to drive gallbladder contraction and vagal satiety signalling.
- Gastrin-34 — The full-length parent peptide; the 34-residue "big gastrin" of which this card covers only the first nine residues; the dominant fasting gastrin form in human plasma.
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.
Would making a ring-shaped version of this fragment work better for generating antibodies that specifically detect the large form of gastrin?
Better antibodies against gastrin-34 specifically would improve blood tests for Zollinger-Ellison syndrome, a rare but serious condition where gastrin-producing tumors cause dangerous overproduction of stomach acid. More specific tests mean earlier and more accurate diagnoses.
Is this 8-amino-acid fragment more locked into a fixed shape than most peptides of similar length?
Unusually rigid short peptides are highly valuable as scaffolds for drug design and as tools to study protein interaction surfaces. If this fragment is conformationally stable, it could be repurposed as a modular building block for new therapeutic peptides.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9182336330413818 | boltz-2 |
| ranking score | 0.797532856464386 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.314 | 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{pep10614,
sequence = {LGPQGPPH},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}