Stress-response research peptide (porcine CRF [1-40; E26, N40])
A pig-derived brain hormone that triggers the body's stress response by telling the pituitary gland to release cortisol; used only as a lab research tool.
- Class
- Porcine hypothalamic peptide (CRF-family)
- Status
- No approved therapeutic status identified
- Best-supported effect
- Not established — the attached source documents sequence identity and porcine origin only; no bioassay, animal, or human evidence is attached to this card
- Main caveat
- Card based on a single catalog-grade source entry with a sequence and one 1986 identity reference; no biological activity, assay, animal, or human data are present
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 peptide is a 40-residue fragment of corticotropin-releasing factor (CRF) isolated from pig (porcine) hypothalami. CRF is a hormone produced in the brain that triggers the body's stress response by telling the pituitary gland to release ACTH, which in turn prompts the adrenal glands to make cortisol. This particular variant — designated [1-40; E26, N40] to indicate glutamate at position 26 and asparagine at position 40 — differs from the canonical human CRF sequence at those two positions, reflecting its porcine origin. Patthy and colleagues (1986) purified it alongside nine other CRF-related polypeptides from porcine hypothalami and confirmed that it stimulates ACTH release from rat pituitary cells. On this platform it is assigned to the CRF receptor type 2 (CRHR2), which mediates anxiolytic and cardioprotective signaling independently of the better-known CRF receptor type 1 (CRHR1).
History
This peptide was identified as part of a landmark biochemical characterization of CRF-related peptides in the pig hypothalamus. Patthy and colleagues (1986) purified ten polypeptides with CRF activity from porcine hypothalami using gel filtration followed by reversed-phase HPLC, and confirmed each by sequence analysis. The work established that multiple CRF-related variants co-exist in the porcine hypothalamus, structurally related to the canonical porcine CRF sequence. The [1-40; E26, N40] designation reflects two amino acid positions that distinguish this variant within that family.
What it does
The peptide stimulates the release of corticotropin (ACTH) from pituitary cells, consistent with its structural relationship to CRF (Patthy et al. 1986). Because the platform assigns it to CRHR2 as its primary receptor, it is used as a research tool to probe CRHR2-mediated biology — including pathways associated with stress recovery, cardiovascular protection, and anxiolytic effects — separately from the CRHR1 pathway that drives the classical HPA-axis stress response.
Evidence
- Human: No human trials identified for this specific CRF variant.
- Animal: Patthy and colleagues (1986) demonstrated ACTH-releasing activity in superfused rat pituitary cells for this peptide and related porcine CRF variants isolated alongside it.
- In vitro: CRF activity confirmed by bioassay (ACTH release from rat pituitary cells) and characterized by sequence analysis (Patthy et al. 1986).
Mechanism
CRF and its analogs act at class B G protein-coupled receptors: CRHR1 and CRHR2. The stored sequence SEEPPISLDLTFHLLREVLEMARAEELAQQAHSNRKLMEN (40 aa) reflects the porcine-origin backbone, with Glu at position 26 and Asn at position 40 distinguishing it from the canonical human CRF-41 sequence. CRHR2 is expressed at lower levels in the pituitary than CRHR1 and is associated with peripheral effects including cardiac stress tolerance and anxiolytic behavior, making CRHR2-selective ligands of interest for dissecting these functions from the CRHR1-driven cortisol axis.
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 swapping one neutral amino acid for a negatively charged one steer a CRF-related peptide away from the acute-stress receptor and toward the calming, heart-protective receptor?
If one amino acid change is enough to redirect activity between these two receptors, it could inspire a straightforward way to design stress-pathway drugs that reduce anxiety and protect the heart without amplifying the acute stress response.
Does the presence of a charged glutamate in the middle of this peptide's helix reduce its rigidity in a way that happens to fit the anxiety-reducing receptor better than the anxiety-driving one?
If natural flexibility from a single substitution can steer a peptide to the desired receptor, it opens a design principle for safer anti-anxiety or cardioprotective drugs that avoid activating the fight-or-flight arm of the stress system.
Does the cluster of negatively charged amino acids at the beginning of this peptide electrostatically attract the positively charged parts of its receptor, speeding up the initial attachment step?
Understanding this docking step could help researchers design CRF-related drugs that work faster or bind more selectively to the anxiety-reducing stress receptor, potentially benefiting people with anxiety disorders or heart failure.
Could this porcine version of CRF, which appears to favor the heart-protective stress receptor, reduce the damage caused when blood flow returns to a heart after a blockage?
If confirmed, this natural peptide variant could become a template for heart attack treatments that protect cardiac muscle during and after a blockage, filling a gap left by existing drugs that activate both beneficial and harmful arms of the stress pathway.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8040639162063599 | openfold3-mlx |
| ranking score | 0.8741033673286438 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.704 | global PDE — lower = better |
| disorder | 0.171 | fraction disordered |
| chain pair ipTM (A, B) | 0.804 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 350s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-22 |
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
@peptide{pep10648,
sequence = {SEEPPISLDLTFHLLREVLEMARAEELAQQAHSNRKLMEN},
target = {crhr2},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}