VIP nerve-hormone fragment (YLNKILNGK)
A tiny synthetic piece of the VIP nerve hormone that latches onto a VIP docking site on cells; used only as a lab research tool, not an approved 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.
What this is
YLNKILNGK is a synthetic 9-amino-acid peptide catalogued in the ChEMBL bioactivity database (CHEMBL3102925) as a ligand for VPAC1 — one of the two main receptors for vasoactive intestinal peptide (VIP), a hormone made by nerves and gut cells that relaxes blood vessels, regulates immune signaling, and helps control smooth-muscle tone. The sequence represents the very C-terminal 9 residues of the native VIP 28-mer, and it is one of the shortest members of a series of VIP C-terminal fragments and analogs characterized by Giordanetto and colleagues (ACS Medicinal Chemistry Letters, 2013). It is a research tool compound, not a marketed drug.
What it does
VPAC1 is a class B G-protein-coupled receptor that, when activated, raises intracellular cAMP through Gαs coupling — the same general signaling family used by PACAP, glucagon, and GLP-1 receptors. The full VIP peptide engages VPAC1 through two regions: the N-terminus, which drives receptor activation, and the central/C-terminal α-helix, which docks into the receptor's large extracellular N-terminal domain (Piper and colleagues, Nature Communications, 2022). Because YLNKILNGK covers only the very C-terminal tail of that helix, it represents a minimal receptor-docking fragment rather than a complete agonist scaffold in the way the full-length VIP is.
History
VIP was first isolated from porcine intestine and signals through two closely related receptors, VPAC1 and VPAC2, both of which are class B GPCRs. Because native VIP binds both receptors with comparable potency and is rapidly degraded in circulation, researchers have explored truncated fragments, alanine-scanning analogs, and backbone-stapled derivatives to understand which portions of the peptide carry binding affinity and how to build receptor-selective or proteolytically stable compounds (Giordanetto and colleagues, ACS Medicinal Chemistry Letters, 2013). YLNKILNGK was deposited in ChEMBL as part of this medicinal-chemistry program alongside longer C-terminal VIP fragments — a 13-mer (pep-10479), a 17-mer (pep-10478), and a 30-mer (pep-10477) — providing a truncation series for understanding the minimal sequence requirements for VPAC1 engagement.
Evidence
- Human: No clinical trials of this specific 9-mer.
- Animal: No in vivo data are present in the dossier for this sequence.
- In vitro: ChEMBL records an EC50 of 0.11 nM at VPAC1 for this peptide, associated with the Giordanetto and colleagues publication (ACS Medicinal Chemistry Letters, 2013). That study characterized a series of lactam-stapled and hydrocarbon-stapled VIP analogs and reported sub-nanomolar potency for the most active variants in functional cAMP assays; the primary focus of the paper was VPAC2 agonism and glucose-dependent insulin secretion.
Related peptides
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| EC50 | 0.11 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.757 | global PDE — lower = better |
| disorder | 0.174 | fraction disordered |
| chain pair ipTM (A, B) | 0.829 | 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 | 373s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
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{pep10480,
sequence = {YLNKILNGK},
target = {vpac1},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}