Peptide YY [3-36]: gut 'I'm full' hormone fragment
A natural gut hormone fragment released after eating that travels to the brain and reduces appetite; the rabbit form is used as a lab research tool.
- Class
- Endogenous peptide fragment
- Status
- No approved therapeutic status identified
- Best-supported effect
- Characterized as a naturally occurring truncated form of peptide YY in rabbit; no functional or therapeutic effect established in this card's source
- Main caveat
- Source file contains sequence and a single species-characterization reference only; no efficacy, receptor, or clinical data are attached
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
Peptide YY [3-36] (PYY[3-36]) is a natural gut hormone fragment that acts as a satiety signal — it tells the brain that the body has eaten enough. The peptide is generated from full-length peptide YY (PYY[1-36]) when the enzyme dipeptidyl peptidase IV (DPP-IV) cleaves the two N-terminal amino acids after the full-length form is secreted into circulation. The sequence stored here — SKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY — is the rabbit form of PYY[3-36]; Grandt and colleagues (1994) were the first to characterize both PYY(1-36) and PYY(3-36) in rabbit intestinal tissue, establishing that rabbit PYY differs from porcine PYY by two amino acid substitutions and from human PYY by one, making the rabbit a useful model for studying PYY biology. PYY belongs to the neuropeptide Y (NPY) peptide family, and its name reflects the tyrosine (single-letter code: Y) residues at both its N- and C-termini — though the active fragment PYY[3-36] retains only the C-terminal tyrosine.
History
PYY was originally isolated from porcine intestinal extracts in 1980. Grandt and colleagues (1994) later characterized two molecular forms — the full-length PYY(1-36) and the truncated PYY(3-36) — in rabbit tissue, purifying the peptide from intestinal mucosa and determining its primary structure. This rabbit characterization was significant because rabbit tissues had been widely used to map PYY receptor subtypes even though the rabbit sequence was still unknown at the time. The discovery that DPP-IV proteolysis converts PYY[1-36] into PYY[3-36] shifted the receptor pharmacology dramatically: the full-length form is a non-selective agonist across the NPY receptor family, whereas the truncated fragment is a highly selective agonist at the Y2 receptor (Y2R/NPY2R), the subtype most relevant to appetite suppression. Interest in PYY[3-36] as a potential obesity therapy intensified in the early 2000s following studies showing that peripheral infusion of postprandial concentrations of the peptide significantly reduced food intake in both lean and obese humans (Karra and colleagues 2009).
What it does
After a meal, L-cells in the distal small intestine and colon release PYY[3-36] in proportion to the caloric content of the food consumed. Plasma levels begin rising within minutes of eating and remain elevated for several hours, helping to prolong the feeling of fullness (Karra and colleagues 2009; Vincent and colleagues 2008). The peptide acts centrally — primarily in the hypothalamus — and peripherally via the vagus nerve to reduce appetite and slow the rate at which the stomach empties. In humans, infusion of PYY[3-36] at normal postprandial concentrations has been shown to significantly reduce food intake over the following 24 hours; notably, obese individuals retain sensitivity to this effect, distinguishing PYY from leptin, to which obese subjects are typically resistant (Karra and colleagues 2009). Beyond appetite, Persaud and colleagues (2014) have reviewed evidence linking PYY to bone metabolism, immune function, and cardiovascular regulation, suggesting a broader physiological portfolio than appetite regulation alone.
Evidence
- Human: Peripheral infusion of PYY[3-36] reduces food intake in both lean and obese human subjects, with obese individuals showing intact Y2R-mediated anorectic responses (Karra and colleagues 2009; Batterham and colleagues reviewed therein). A small clinical study reported that high-dose infusions caused nausea in a majority of participants, limiting the dose range at which the peptide is well tolerated. Combined administration with GLP-1(7-36) amide reduced food intake additively in overweight humans (Silva and colleagues 2012).
- Animal: Y2 receptor knockout mice are fully resistant to the anorectic effect of PYY[3-36], establishing the Y2R as the necessary mediator; PYY-deficient mice develop obesity that is reversed by PYY[3-36] replacement (Karra and colleagues 2009). Rodent models of diet-induced obesity show reduced food intake and weight after peripheral PYY[3-36] administration.
- In vitro: Electrophysiology studies in the arcuate nucleus demonstrate that PYY[3-36] directly inhibits the firing of NPY/AgRP neurons via postsynaptic Y2 receptors and activates POMC neurons, shifting the hypothalamic balance from hunger-promoting to satiety-promoting signalling (Karra and colleagues 2009).
Known effects
- Appetite suppression — Preclinical and human studies; requires intact Y2 receptor signalling
- Gastric emptying delay — Documented in human studies at physiological concentrations (Vincent and colleagues 2008)
- Postprandial satiety prolongation — Physiological role; levels rise with meal caloric content (Karra and colleagues 2009)
- Additive satiety with GLP-1 — Human infusion data; complementary hypothalamic pathways (Silva and colleagues 2012)
- Possible roles in bone, immune, and cardiovascular regulation — Under active investigation; reviewed by Persaud and colleagues (2014)
Safety signals
Dose-dependent nausea is the primary adverse effect reported in human infusion studies. At higher infusion rates, a majority of subjects experienced nausea severe enough to require termination of the infusion; lower doses were generally better tolerated (Karra and colleagues 2009). An intranasal formulation developed for obesity treatment showed gastrointestinal adverse events as the main tolerability concern in clinical testing, and the Phase 2 trial of a nasal spray formulation did not meet its weight-loss primary endpoint. A long-acting PYY[3-36] analogue studied in combination with semaglutide (2025 clinical data) showed modest additional weight loss but significant GI tolerability issues at higher doses. PYY[3-36] is not approved as a drug in any jurisdiction. No human trials have been completed for the rabbit sequence variant specifically; most clinical work has used the human/porcine sequence.
Regulatory status
- US: Not FDA-approved. Investigational only. No IND-active programme known for the rabbit sequence specifically.
- EU: Not EMA-approved.
- WADA: PYY[3-36], as a peptide hormone with appetite-modifying effects, falls within the class of peptide hormones subject to WADA's general prohibition framework; specific listing status should be verified in the current WADA Prohibited List.
Related peptides
- PYY[1-36] — the full-length precursor; non-selective Y-receptor agonist; converted to PYY[3-36] by DPP-IV in circulation
- Neuropeptide Y (NPY) — the family prototype; shares the C-terminal "PP-fold" structure; endogenous orexigenic peptide acting at Y1 and Y5 receptors
- Pancreatic Polypeptide (PP) — a third NPY-family member released postprandially from the pancreas; Y4-receptor selective; reviewed alongside PYY[3-36] in appetite biology (Silva and colleagues 2012; Persaud and colleagues 2014)
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.
Is the receptor listed for this peptide a mistake, and does PYY[3-36] actually work through the well-known Y2 receptor?
If the annotation is wrong, correcting it would point research at the right target. The NPBWR1 label here looks like an automated mis-assignment shared across several PYY and NPY family entries; the published references all describe PYY[3-36] as a selective Y2 receptor agonist.
Could this appetite-suppressing peptide also affect patients whose stomachs empty too slowly, such as people with diabetes-related gastroparesis?
PYY[3-36] is documented to slow stomach emptying, and Y2 receptors are present on gut nerves, so a peripheral motility effect is plausible. Whether it could help or worsen a specific motility disorder is unknown and would need direct study, but it points to a question worth investigating beyond appetite.
Is the rabbit version of this satiety peptide close enough to the human version that the receptor it acts on responds the same way?
The single difference between the rabbit and human forms sits at the far N-terminal end, away from the C-terminal region that contacts the Y2 receptor, so the two forms may be similar at that receptor. If borne out, this would help interpret older rabbit-based studies, though it has not been directly tested.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9341727495193481 | boltz-2 |
| ranking score | 0.8670646548271179 | boltz-2 |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10655,
sequence = {SKPEAPGEDASPEELNRYYASLRHYLNLVTRQRY},
target = {npbwr1},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}