pe
pep-10372 v1 CC-BY-SA-4.0

Gut-healing peptide (CHEMBL3824227)

A lab-made peptide that activates the gut receptor responsible for intestinal repair and growth; experimental, not yet an approved drug.

statusbioassayed targetGLP-2R length27 aa refs2
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 5 / 5
prediction metrics openfold3-mlx 0.3.1
ipTM0.874
pTM0.680
avg pLDDT49.2
ranking score0.957
STRUCTURE · PEP-10372 × GLP-2R
ranking0.957
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
openfold3-mlx 0.3.1 · mmCIF ↓ download
sequence27 aa
151015202527
HGDGSFSDE MNTILDNLA ARDFINWLI
in the news 1 article
Hypotheses2 directions▾ collapse

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.

openupdated 2026-06-11

Does the one altered building block in pep-10372 protect it from DPP-4, the enzyme that chops up and inactivates gut signals like GLP-2?

If the peptide survives longer in the body, patients with short bowel syndrome might need fewer or smaller injections to repair their gut lining. The same single change gives the approved drug teduglutide its staying power, so this is well supported rather than a sure thing.

The hypothesis
pep-10372 acts as a more proteolytically stable GLP-2R agonist than native GLP-2 because the Gly2 substitution reduces DPP-4 cleavage at the His1-Gly2 bond, which is the primary inactivation site for native GLP-2 (His1-Ala2).
Why it’s plausible
DPP-4 cleaves GLP-2 at the His-Ala bond at positions 1-2, generating inactive GLP-2(3-33). The A2G substitution in pep-10372 replaces Ala with Gly; while both are small, structural studies show DPP-4 accommodates Ala much more readily than Gly in the S1 pocket due to van der Waals fit. This single substitution is the basis for the FDA-approved GLP-2 analog teduglutide (A2G), supporting this hypothesis.
Why it matters
Resistance to DPP-4 would dramatically extend the in vivo half-life of pep-10372, making it suitable for less-frequent dosing. This is directly therapeutically relevant for short bowel syndrome and other intestinal insufficiency conditions where sustained GLP-2R stimulation is needed.
Plausibility.90
Novelty.15
Impact.70
Basis · grounding1 paper · 2 computed/notes
[1]
sequencePosition 2 is Gly (HGDGSFSDEM...) matching the teduglutide A2G substitution that confers DPP-4 resistance
[2]
paper
Native GLP-2 acts on the full GI tract; rapid DPP-4 inactivation limits its half-life, making DPP-4-resistant analogs therapeutically significant
doi: 10.1210/jcem.86.4.7386
[3]
notePeptide is named 'gut-healing peptide' (CHEMBL3824227), consistent with a designed GLP-2 analog optimized for therapeutic intestinal action
openupdated 2026-06-11

Does pep-10372 shift from a floppy to a structured form once it docks onto the GLP-2 receptor?

Peptides that fold only at their target can be harder for the body to break down in transit, which could make for longer-lasting gut medicines and better treatments for conditions like short bowel syndrome or Crohn's disease.

The hypothesis
The Gly substitution at position 2 (His-Gly vs. His-Ala in native GLP-2) destabilizes the N-terminal alpha-helix, causing pep-10372 to adopt a more disordered free-form conformation than native GLP-2, yet the high ipTM (0.874) indicates this disorder is resolved upon receptor binding, suggesting an induced-fit mechanism for GLP-2R activation.
Why it’s plausible
pLDDT of 49.2 signals intrinsic disorder in the unbound peptide, while ipTM 0.874 indicates confident receptor-bound complex. Gly at position 2 lacks the methyl side-chain of Ala, reducing helical propensity. Native GLP-2 is known to adopt a helix upon receptor engagement. Together these data point to disorder-to-order folding at GLP-2R as the functional trigger.
Why it matters
If true, pep-10372 exploits conformational plasticity to achieve selectivity. Disordered peptides can be more cell-permeable and proteolytically stable in free form, then fold on-target. This mechanism would distinguish pep-10372 from native GLP-2 and inform design of next-generation gut-healing peptides with improved pharmacokinetics.
Plausibility.55
Novelty.30
Impact.45
Basis · grounding1 paper · 2 computed/notes
[1]
structureipTM=0.874 (high confidence bound complex) contrasted with pLDDT=49.2 (low confidence free-form structure), consistent with disorder-to-order transition on binding
[2]
sequencePosition 2 is Gly (HGDGSFSDEM...) rather than Ala as in native GLP-2 (HADGSFSDEM...), reducing helical propensity at the N-terminus
[3]
paper
GLP-2 acts on the full GI tract through GLP-2R, establishing the receptor-binding context for this structural comparison
doi: 10.1210/jcem.86.4.7386
details expand to inspect
full evidence table1 metrics
metricvaluetool
EC50 1.1 nM GPCRDB/ChEMBL
structural qualityopenfold3
0
metricvaluenote
gpde0.734global PDE — lower = better
disorder0.243fraction disordered
chain pair ipTM (A, B)0.874interface quality
3-letter notation
His-Gly-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile
recipeopenfold3-mlx 0.3.1
parametervalue
modelopenfold3-mlx 0.3.1
weightsaedd8f3eb814e392…
hardwareapple_m4_base_16gb
mlx version0.31.1
python3.14.3
random seed42
msa strategycolabfold
diffusion samples1
runtime634s
predicted bymlx@peptide
predicted at2026-04-22
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1
citationbibtex
peptidemodel (2026). Gut-healing peptide (CHEMBL3824227) (pep-10372, v1). PeptideModel. https://peptidemodel.com/card/pep-10372
@peptide{pep10372,
  sequence = {HGDGSFSDEMNTILDNLAARDFINWLI},
  target   = {glp-2r},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
clinical trials 0 trials · checked 2026-05-22
0
no registered clinical trials as of 2026-05-22; we'll re-check periodically
references 2 papers
[1] supporting
[2]
Glucagon-Like Peptide 21
Drucker, D. The Journal of Clinical Endocrinology & Metabolism 2001
supporting
discussion no comments
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