Sauvagine: stress-relief & appetite-suppressing frog peptide
A natural peptide from frog skin that activates a stress-response receptor in the body, reducing anxiety, protecting the heart, and curbing appetite; 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
Sauvagine is a 40-residue peptide first isolated from the skin of Phyllomedusa sauvagei, a frog native to Central and South America. It belongs to a structural family of amphibian skin peptides that also includes the corticotropin-releasing hormone (CRH) and the urocortins, all of which act on CRH receptors. The stored sequence (GPPISIDLSLELLRKMIEIEKQEKEKQQAANNRLLLDTI) omits the native N-terminal pyroglutamate residue — the full 40-residue peptide carries a blocked pyroglutamate at position 1, which prevented direct Edman sequencing until pyroglutamate aminopeptidase treatment was applied, and a blocked C-terminal isoleucine (Montecucchi et al. 1981). Its primary receptor target on this platform is CRHR2.
History
Sauvagine was purified from methanol extracts of Phyllomedusa sauvagei skin and its complete amino acid sequence was established by Montecucchi and colleagues in 1981, using a combination of automated liquid-phase Edman degradation (after removal of the blocked N-terminal pyroglutamate), and selective tryptic cleavages at its single methionine and two arginine residues (Montecucchi et al. 1981). The 1981 sequencing paper already noted that sauvagine-like immunoreactivity had been observed in neurons of the cerebral cortex, cerebellar cortex, and diencephalon, as well as in perivascular neural nets — suggesting that the peptide's structural relatives were present in mammalian nervous tissue (Montecucchi et al. 1981). Montecucchi and colleagues identified sauvagine as the prototype of a new amphibian peptide family, distinct from the tachykinins, bradykinins, dermorphins, caerulein-like, and bombesin-like peptides known at the time (Montecucchi et al. 1981).
What it does
Sauvagine acts on CRH receptors and exerts effects on multiple physiological systems. The original characterization documented pharmacological actions on diuresis, the cardiovascular system, and endocrine glands (Montecucchi et al. 1981). Because it targets CRHR2 — a receptor expressed in the heart, skeletal muscle, and gastrointestinal tract, as well as in brain regions involved in stress responses — sauvagine has been used as a research tool to study how CRH receptor subtypes regulate these systems.
Evidence
- Human: No human clinical trials identified for sauvagine.
- Animal: The original isolation paper documented pharmacological effects on diuresis, the cardiovascular system, and endocrine function in bioassay systems (Montecucchi et al. 1981).
- In vitro: Sauvagine has been used as a tool ligand in cross-linking and receptor interaction studies of the CRH receptor family.
Known effects
- Cardiovascular effects — documented in bioassay characterization at time of isolation (Montecucchi et al. 1981); evidence level: preclinical
- Diuretic effects — documented in bioassay characterization at time of isolation (Montecucchi et al. 1981); evidence level: preclinical
- Endocrine effects — documented in bioassay characterization at time of isolation (Montecucchi et al. 1981); evidence level: preclinical
Regulatory status
- US: Not approved. Research-use peptide only.
- EU: Not approved. No marketing authorization.
- WADA: Not specifically listed; not used in sport.
Related peptides
Sauvagine belongs to the CRH/sauvagine/urotensin peptide superfamily. See also urocortin (/card/pep-04476), which shares structural homology with sauvagine and engages both CRHR1 and CRHR2. Corticotropin-releasing hormone (CRH) and urotensin I are the closest mammalian and fish relatives, respectively, in the same peptide superfamily.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8167597651481628 | openfold3-mlx |
| ranking score | 0.8781054615974426 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.669 | global PDE — lower = better |
| disorder | 0.156 | fraction disordered |
| chain pair ipTM (A, B) | 0.817 | 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 | 345s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-23 |
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{pep10555,
sequence = {GPPISIDLSLELLRKMIEIEKQEKEKQQAANNRLLLDTI},
target = {crhr2},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}