Stress-hormone research tool (CRF [1-40; Met30-oxidized, Ile40])
A lab-made variant of the body's main stress-signaling hormone, used to study how stress receptors recognize their triggers; not a drug, used only as a lab research tool.
- Class
- Porcine CRF variant / neuropeptide fragment
- Status
- Research or catalog entry; no approved therapeutic status identified
- Main caveat
- This card describes a chemically characterized porcine CRF peptide fragment with an oxidized methionine at position 30; no bioactivity, pharmacological, or clinical evidence is attached to this card's source file.
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
CRF [1-40; Met30-oxidized, Ile40] is a synthetic 40-residue peptide based on the porcine corticotropin-releasing factor sequence. Corticotropin-releasing factor (CRF, also called CRH) is the hypothalamic hormone that sits at the top of the stress-response axis: it signals the pituitary to release ACTH, which in turn drives cortisol production from the adrenal glands. This particular variant carries an oxidized methionine at position 30 — meaning the sulfur in that residue has been oxidized — and terminates with isoleucine at position 40, features that distinguish it from human CRF and mark it as a tool for studying how the CRF receptor family recognizes its ligands. The stored sequence SEEPPISLDLTFHLLREVLEMARAEQLAQQAHSNRKLMEI is the full 40-residue backbone; the Met30 oxidation is not visible in the single-letter code but is chemically present in the synthesized peptide.
History
The porcine CRF sequence that underlies this peptide was characterized in 1986 by Patthy and colleagues, who isolated and purified ten polypeptides with corticotropin-releasing activity from porcine hypothalami (Patthy et al., Proceedings of the National Academy of Sciences, 1986). That study used gel filtration followed by reversed-phase HPLC to separate CRF-related peptides from pig hypothalamic extracts and confirmed CRF activity by measuring ACTH release from superfused rat pituitary cells. The oxidized methionine variant described on this card was among the structurally characterized polypeptides identified in that purification work.
What it does
This peptide is a research tool rather than a therapeutic or physiological agent in its own right. It is used to probe ligand binding and receptor activation at CRHR2 (corticotropin-releasing hormone receptor 2), one of the two main receptor subtypes in the CRF family. By comparing how the oxidized Met30 variant interacts with CRHR2 relative to unmodified CRF, researchers can investigate how methionine oxidation — a common post-synthetic modification and potential oxidative damage event — affects receptor engagement.
Evidence
- Human: No clinical trials. This is a research-grade synthetic peptide used in binding and receptor characterization studies, not a drug or clinical agent.
- Animal: Functional activity established via rat pituitary superfusion assay, where CRF-related peptides isolated from porcine hypothalami stimulated ACTH release (Patthy et al. 1986).
- In vitro: CRHR2 binding probe in pharmacological receptor characterization studies.
Mechanism
CRF peptides act on class B G protein-coupled receptors (GPCRs). CRHR2 is expressed in peripheral tissues including the heart, skeletal muscle, and gastrointestinal tract, as well as in subcortical brain regions, and has distinct ligand preferences from CRHR1 — it is the primary receptor for the urocortin 2 and urocortin 3 peptides under physiological conditions. Synthetic CRF analogs based on the full 40-residue porcine sequence, including this oxidized variant, can engage CRHR2 and have been used to examine how structural features of the ligand — including modifications such as methionine oxidation — alter receptor binding affinity and functional signaling. The oxidation of Met30 introduces a sulfoxide group that changes local side-chain polarity and steric properties in a region of the peptide that contributes to helix stability and receptor contact, providing a defined chemical perturbation for structure-activity studies.
Related peptides
- Urocortin 2 and urocortin 3 are the endogenous selective CRHR2 agonists that this synthetic variant is used alongside in receptor characterization.
- Human CRF [1-41] — the full-length endogenous hypothalamic peptide that acts on both CRHR1 and CRHR2.
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 a peptide carrying both oxidized modifications, one from each of two known CRHR2-selective analogs, be even more specific for the calming stress receptor?
A more selective research tool would let scientists study the stress-recovery receptor's role in heart disease, mood disorders, and appetite regulation without any background noise from the anxiety receptor, accelerating the discovery of targeted therapies for these conditions.
Does the stiff double-proline segment near the beginning of this stress hormone act like a hinge that lets the two ends of the peptide independently find their receptor contacts?
If the hinge is confirmed, pharmaceutical chemists could fix its angle to lock the peptide in a receptor-selective shape, providing a rational engineering principle for the entire CRF drug family including potential treatments for anxiety, PTSD, and stress-related disorders.
Does chemically altering amino acid 30 in this stress hormone cause it to avoid the anxiety receptor and prefer the calming recovery receptor?
If Met30 is confirmed as a selectivity switch, drug designers could use it alongside other known switches to fine-tune new stress-hormone analogs, potentially yielding more precise treatments for anxiety, post-traumatic stress, and stress-related heart conditions.
Is porcine CRF already naturally biased toward the calming stress receptor because it lacks the chemical cap that human CRF uses to grip the anxiety receptor?
If porcine and human stress hormones preferentially activate different receptors due to a simple length difference, researchers using porcine CRF in cell assays may be drawing incorrect conclusions about human stress biology, and fixing this understanding could improve the reliability of drug discovery programs.
Could this modified porcine stress hormone help protect the heart during cardiac stress events without triggering the anxiety side effects caused by activating the other stress receptor?
If confirmed, this could lead to a new class of heart-protective drugs based on the body's own stress-hormone chemistry, offering cardiac protection during heart attacks or surgery with fewer psychiatric side effects than current approaches.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7978164553642273 | openfold3-mlx |
| ranking score | 0.8688949942588806 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.720 | global PDE — lower = better |
| disorder | 0.173 | fraction disordered |
| chain pair ipTM (A, B) | 0.798 | 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 | 349s |
| 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{pep10649,
sequence = {SEEPPISLDLTFHLLREVLEMARAEQLAQQAHSNRKLMEI},
target = {crhr2},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}