Kidney-water-retaining peptide (Arg8,des-Gly-NH2⁹-vasopressin)
A lab-made version of the body's natural water-retention hormone, tweaked to act mainly on the kidney; used only as a research tool, not an approved 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
(Arg8,des-Gly-NH2⁹)-vasopressin — sometimes written as [Arg8,des-Gly9-NH2]-AVP — is a synthetic, eight-residue analog of arginine vasopressin (AVP), the natural antidiuretic hormone produced in the hypothalamus. The modification is a deletion of the C-terminal glycine-amide found in native AVP, leaving Arg8 as the new C-terminus; the Cys1–Cys6 disulfide ring that gives vasopressin its characteristic cyclic structure is retained. The stored sequence CYFQNCPR is a single-letter approximation: the disulfide bond between positions 1 and 6 closes a ring that is not visible in the linear notation. This compound has no approved clinical use and is used primarily as a pharmacological tool to study vasopressin receptor subtypes and antidiuretic signaling.
What it does
Vasopressin acts on three receptor subtypes — V1aR (vasoconstriction), V1bR (pituitary/stress axis), and V2R (kidney water reabsorption). The removal of the C-terminal Gly-NH2 group from native AVP is a structural modification that has been reported to alter receptor subtype selectivity relative to the parent molecule. The V2 receptor in kidney collecting-duct principal cells controls water reabsorption by triggering translocation of the water channel aquaporin-2 (AQP2) to the apical membrane (Robben et al., 2004; Goel et al., 2010). This process is driven by the cAMP/PKA signaling cascade downstream of V2R (Goel et al., 2010). At V2R, vasopressin analogs also stimulate release of von Willebrand factor (vWF) and coagulation factor VIII — a hemostatic effect exploited clinically by desmopressin, the FDA-approved V2R-selective analog (Nakamura et al., 2000).
Evidence
- Human: No human clinical trials are registered or published for (Arg8,des-Gly-NH2⁹)-vasopressin specifically.
- Animal: Vasopressin processing intermediates with the sequence CYFQNCPRGGKR — the biosynthetic precursor that includes this octapeptide core — have been quantified in mouse pituitary using stable-isotope peptidomics (Che et al., 2005), establishing that carboxypeptidase E cleavage generates such C-terminally truncated forms in vivo.
- In vitro: The pharmacological framework for interpreting V2R-selective analogs is grounded in cell-based studies: Nakamura and colleagues (2000) characterized V2R, V1aR, and V1bR binding and functional responses in transfected HeLa cells, comparing the peptide V2R agonist dDAVP (desmopressin) against a nonpeptide agonist; Robben and colleagues (2004) studied V2R regulation in a polarized renal collecting-duct cell line stably expressing V2R-GFP.
Mechanism
Native AVP (CYFQNCPRG-NH₂, 9 aa) binds V2R in the basolateral membrane of kidney collecting-duct principal cells, activating adenylyl cyclase and raising intracellular cAMP. PKA phosphorylation of aquaporin-2 (AQP2) vesicles drives their insertion into the apical membrane, increasing transepithelial water permeability (Robben et al., 2004). The cAMP/PKA axis also traffics TRPC3 channels to the apical membrane in concert with AQP2 (Goel et al., 2010). Removal of the C-terminal Gly9-NH2 — yielding the CYFQNCPR octapeptide — alters the C-terminal pharmacophore that contacts the receptor extracellular loops, with the consequence of changed receptor-subtype selectivity relative to native AVP. The Cys1–Cys6 disulfide bond, which constrains the N-terminal ring essential for receptor recognition across the vasopressin/oxytocin family (Möller et al., 2007), is preserved in this analog. Structurally, the compound is most closely related to natural vasotocin variants (CYIQNCPRG) found in non-mammalian vertebrates, which share the same ring motif (Möller et al., 2007).
Neuropeptides of the vasopressin family, including AVP itself, have also been noted as candidates in the search for anticonvulsant mechanisms (Clynen et al., 2014), though this application has not been explored for the des-Gly analog specifically.
Known effects
- Antidiuretic (V2R-mediated AQP2 trafficking) — Mechanistic / preclinical framework; no clinical data for this specific analog
- Hemostatic (vWF/FVIII release) — Established for V2R agonists as a class; not directly measured for this analog
- Receptor subtype tool compound — Used to dissect V1aR vs V2R pharmacology in binding and functional assays
Regulatory status
- US: Not approved. Investigational/research compound only.
- EU: Not approved.
- WADA: Vasopressin and structural analogs fall within the category of peptide hormones on the WADA Prohibited List; research use does not imply sanctioned athletic use.
Related peptides
- Desmopressin — [deamino-Cys1, D-Arg8]-AVP; the FDA-approved V2R-selective agonist used clinically for diabetes insipidus, von Willebrand disease, and nocturnal enuresis. The benchmark comparator for V2R selectivity in the vasopressin analog series (Nakamura et al., 2000).
- Arginine vasopressin (AVP) — The native 9-residue nonapeptide (CYFQNCPRG-NH₂) of which this compound is a C-terminal truncation; avpr1a and avpr2 are its primary targets.
- Oxytocin — The closely related nonapeptide (CYIQNCPLG-NH₂) sharing the Cys1–Cys6 disulfide ring scaffold; diverges at positions 3, 4, and 8 from AVP, producing selective oxytocin-receptor rather than vasopressin-receptor activity.
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.
If we add back only the amide group at the tip of this peptide, without the extra amino acid, does it behave like the natural hormone again?
Answering this question would give drug designers a precise chemical rule for tuning vasopressin-like peptides, potentially speeding up development of more targeted treatments for water balance disorders and bleeding conditions.
Does removing the last amino acid turn vasopressin from a full activator into a partial one in kidney cells?
If the peptide is a partial activator, it could produce controlled, moderate water retention rather than a full antidiuretic response, which might be useful for conditions needing gentle fluid balance adjustment. It would also reveal a key chemical rule for designing safer vasopressin-based drugs.
Does the free arginine at the end of this truncated peptide fold back onto its own ring, changing the molecule's overall shape?
If confirmed, this would explain why small changes at the end of vasopressin-like peptides can have outsized effects on how they behave, giving drug designers a clearer map for building better, more targeted versions of this hormone.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9247241616249084 | boltz-2 |
| ranking score | 0.7204251289367676 | 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{pep10514,
sequence = {CYFQNCPR},
target = {avpr1a},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}