Lab peptide that grabs a muscle-signal receptor (DTVGL / CHEMBL103634)
A tiny five-piece synthetic peptide that latches onto a receptor found on smooth muscle in the airways and gut; used only as a research tool, not a medicine.
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
DTVGL (CHEMBL103634) is a synthetic five-residue peptide that binds to the NK-2 receptor — a protein found on smooth muscle, airway, and gut cells that responds to the neuropeptide neurokinin A. It was characterized as part of a structure-activity study on truncated and modified analogs of neurokinin A, a naturally occurring signaling peptide in the tachykinin family. DTVGL is a research compound; it has no approved clinical use.
What it does
The NK-2 receptor (encoded by TACR2) is a G protein-coupled receptor whose principal endogenous activator is neurokinin A. When neurokinin A or an agonist binds, the receptor couples to Gαq, triggering phospholipase C activation, IP3 release, and a rise in intracellular calcium — effects that translate physiologically into smooth muscle contraction, bronchoconstriction, and modulation of gut motility. DTVGL binds the NK-2 receptor with an IC50 of 107.15 nM (Gembitsky and colleagues 1999).
That potency is roughly in line with what would be expected for a fragment lacking the aromatic phenylalanine at position 6 of the neurokinin A (4–10) pharmacophore. Structure-activity work on NKA(4–10) analogs has established that the position-6 aromatic side chain is the single most important determinant of NK-2 receptor affinity: substituting it reduces binding by approximately 5000-fold compared to the intact sequence (Warner and colleagues 2001). DTVGL retains the C-terminal Gly-Leu residues that contribute to receptor contacts within the transmembrane binding cavity, which likely accounts for its measurable, if modest, affinity.
Evidence
- Human: No human studies. DTVGL is a pharmacological characterization compound, not a clinical candidate.
- Animal: Not reported in available literature.
- In vitro: IC50 = 107.15 nM at the NK-2 receptor (TACR2), measured in the binding study reported by Gembitsky and colleagues (1999).
Mechanism
The NK-2 receptor belongs to the rhodopsin-superfamily of GPCRs and preferentially binds neurokinin A over substance P or neurokinin B (rank order: NKA > NKB >> SP). Cryo-EM analysis of the NK2R–Gq–NKA ternary complex at 2.7 Å resolution showed that the conserved C-terminal residues of NKA insert into the transmembrane cavity, where Val7, Leu9, and Gly8 of NKA form hydrogen bonds with receptor residues on TM2, TM3, and TM7 (Sun and colleagues 2022). Receptor activation cascades through the toggle-switch residues and outward displacement of TM6, opening the intracellular face to Gq coupling.
DTVGL covers only five residues and lacks the full address-message architecture of the natural ligand; the Asp-Thr dipeptide at its N-terminus replaces the Asp-Ser-Phe triad of NKA(4–6) without the critical phenylalanine. Its binding, assessed at 107.15 nM, reflects partial engagement of the C-terminal message region rather than a complete agonist interaction. Whether DTVGL is a partial agonist or a weak full agonist at NK-2 has not been characterized in functional assays in the available literature.
Open questions
- Functional status (full agonist vs. partial agonist vs. antagonist) at NK-2 has not been established in published data.
- Selectivity over NK-1 (TACR1) and NK-3 (TACR3) receptors has not been reported.
- No pharmacokinetic data (serum half-life, proteolytic stability) are available for this sequence.
- Structural basis of binding — whether the Asp-Thr N-terminal dipeptide makes productive contacts with the NK-2 extracellular loops — has not been directly resolved.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| IC50 | 107.15 nM | GPCRDB/ChEMBL |
▸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{pep10459,
sequence = {DTVGL},
target = {tacr2},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}