26RFa brain-signaling peptide
A naturally occurring neuropeptide that activates a poorly understood brain receptor (SP9155); studied only in lab experiments, not yet a drug.
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.
Snapshot
Class: Endogenous RFamide neuropeptide ligand
Evidence tier: In vitro / assay evidence
Status: Research peptide; no approved therapeutic status identified
Best-supported effect: Receptor binding and activation of orphan GPCR SP9155 in characterization assays (in vitro)
Main caveat: Evidence is limited to the original receptor-identification study; no animal or human data identified
What this is
P517 (KKGGFSFRF-NH2) is a 9-residue RFamide peptide of human origin identified as a ligand for the orphan G-protein-coupled receptor SP9155. It was characterized in a 2003 receptor-deorphanization study and belongs to the broader RFamide neuropeptide family, which shares the conserved C-terminal Arg-Phe-NH2 motif. No therapeutic application, animal efficacy model, or human study is identifieds available literature.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None identified | No human trial or observational evidence is identifieds available literature |
| Animal | None identified | No animal experiment evidence is identifieds available literature |
| In vitro | Weak | Receptor identification and ligand characterization for SP9155 in cell-based assays (Jiang et al. 2003) |
| Computational | None identified | No computational or structural prediction data is identifieds available literature |
| Mechanism | Plausible | RFamide GPCR agonism inferred from receptor-identification assay results; downstream pathway not characterized in attached source |
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Binds and activates orphan GPCR SP9155 | Supported (in vitro) | In vitro | Medium — single characterization study; no independent replication identified in source |
| Any therapeutic or physiological role in humans | Not established | None | Low — no human, animal, or mechanistic downstream data identifieds available literature |
| Receptor selectivity beyond SP9155 | Not established | None | Low — selectivity profile not described in attached source |
Assay conditions
This section reports conditions used in the receptor-identification assay. It does not establish animal or human exposure.
| Context | System | Assay condition | Timepoint | Endpoint | Limitation |
|---|---|---|---|---|---|
| Orphan GPCR characterization | Cell-based receptor assay (SP9155-expressing cells) | Peptide applied at assay concentrations; exact concentration not extracted from source | Not specified in source | Receptor binding and activation of SP9155 | Single study; no independent replication identified; conditions not individually extracted |
Assay limitations
- Evidence is derived from a single receptor-identification and characterization study; independent replication is not present.
- No animal toxicology or human safety data are identified.
- In vitro receptor activity does not establish systemic tolerability, bioavailability, or physiological relevance.
- The downstream signaling pathways activated by SP9155 following P517 binding are not characterized in the attached source.
Mechanism
P517 acts as a ligand for SP9155, an orphan G-protein-coupled receptor. The RFamide C-terminal motif (Arg-Phe-NH2) is shared across the RFamide neuropeptide family and is generally associated with GPCR recognition, though the specific signaling cascade downstream of SP9155 activation is not described in available literature. The receptor target is verified by the characterization study; the broader physiological or pharmacological significance of this interaction remains uncharacterized in the attached source.
Chemistry
| Field | Value |
|---|---|
| Amino-acid chain | KKGGFSFRF |
| Full IUPAC notation | H-Lys-Lys-Gly-Gly-Phe-Ser-Phe-Arg-Phe-NH2 |
| Length | 9 amino acids |
| Topology | Linear |
| C-terminal modification | Amidation (–NH2) |
| Species of origin | Human (Homo sapiens) |
| Molecular weight | Not extracted from source |
| Formula | Not extracted from source |
| CAS | Not extracted from source |
| Sequence confidence | Needs review — source is single catalog entry; not cross-checked against primary sequence databases in this card |
Open questions
- Physiological role: The biological function of P517 and SP9155 in human physiology has not been characterized in the attached source. What tissue or circuit context is relevant?
- Receptor deorphanization completeness: SP9155 is described as an orphan GPCR; whether it has since been fully characterized or renamed is not addressed in the attached source.
- Selectivity profile: Whether P517 is selective for SP9155 over other RFamide receptors (e.g., NPFF receptors, QRFP receptor) is not established in the attached source.
- Downstream signaling: The G-protein coupling and intracellular signaling pathway activated by SP9155 upon P517 binding are not described.
- Animal and human translation: No animal model or human evidence is identified; whether the receptor interaction has physiological or pharmacological significance in vivo is unknown.
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 KKGGFSFRF actually acting on opioid receptors, or does it target a different family of brain receptors that modify how opioids work?
Getting the receptor right changes the entire drug development strategy: if this peptide modifies opioid signaling indirectly, it could be developed to reduce opioid side effects like tolerance and addiction without being an opioid itself, which would be highly valuable clinically.
Could this small neuropeptide fragment activate the brain receptor that triggers hunger and food-seeking behavior?
If this peptide activates the hunger-regulating QRFPR receptor, it could provide a minimal scaffold for developing treatments for conditions where stimulating appetite is critical, such as cancer-related weight loss, chemotherapy-induced anorexia, or wasting diseases.
Does the serine in the middle of this peptide make it selectively activate one hunger-regulating brain receptor rather than the pain-signaling receptors in the same family?
A peptide that selectively activates QRFPR without activating NPFF receptors could be used to study appetite regulation without confounding effects on pain and opioid signaling, and could potentially be developed into a more targeted drug for metabolic or eating disorders.
Do the two positively charged amino acids at the front of this peptide help it concentrate near cell surfaces, making it more potent at activating its receptor?
If the membrane-anchoring role of the diLysine is confirmed, drug designers could engineer more potent analogs by tuning this electrostatic patch, potentially leading to lower effective doses of any therapeutic derived from this peptide family.
Does the flexible middle section of this peptide act as a joint that allows the pharmacophore end to swing into different receptor-binding positions?
If the glycine hinge controls receptor selectivity, chemists could design modified versions with a rigid hinge that preferentially activate the appetite receptor rather than pain receptors, providing more targeted drugs with fewer side effects for metabolic disorders.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9417022466659546 | boltz-2 |
| ranking score | 0.8153480887413025 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.064 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10611,
sequence = {KKGGFSFRF},
target = {oprm1},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}