Lysine vasopressin: water-retention hormone variant
A lab-made version of vasopressin, the body's natural water-regulating hormone, modified to reduce blood-pressure-raising effects while keeping its water-retention action; used only as a lab research tool.
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
(Lys8)-Vasopressin is a synthetic analog of the natural hormone vasopressin (also called arginine vasopressin or ADH), in which the arginine at position 8 of the native nine-amino-acid sequence is replaced by lysine. Like natural vasopressin, it is a cyclic nonapeptide; the stored sequence CYFQNCPKG encodes the backbone but does not show the disulfide bond between Cys1 and Cys6 that closes the ring, nor the C-terminal glycine amide (-NH₂) that caps the molecule — both of which are present in the active peptide and shared across the vasopressin/oxytocin family (Möller et al., 2007). The analog was first synthesized to probe how substitutions at position 8 alter the balance between the hormone's two main pharmacological actions: its antidiuretic (water-retaining) effect at the kidney and its pressor (blood-pressure-raising) effect at blood vessels.
History
Zaoral and colleagues synthesized (Lys8)-Vasopressin — alongside the D-Arg8 variant — in 1967, reporting both compounds in the Czech journal Collection of Czechoslovak Chemical Communications (Zaoral et al., 1967). The synthesis was part of the broader mid-twentieth-century effort to map the structure–activity relationships of vasopressin and oxytocin after Vincent du Vigneaud's group established the parent sequences. Position 8 was recognized early as a key determinant of receptor selectivity: natural vasopressin carries L-Arg at that site, while the related hormone oxytocin carries L-Leu, and the therapeutically important analog desmopressin uses D-Arg. Exploring Lys at position 8 was a logical step in understanding how the side-chain chemistry at that residue shapes pressor versus antidiuretic activity.
What it does
(Lys8)-Vasopressin acts at vasopressin receptors, with the lysine substitution shifting activity relative to the native arginine-containing hormone. The card's receptor assignments reflect this: the V1a receptor (avpr1a), which mediates vasoconstriction in blood vessels, is the primary listed target, with the V2 receptor (avpr2), which drives water reabsorption in the kidney collecting duct, listed as secondary. The V2 pathway operates through a cyclic AMP cascade that triggers aquaporin-2 water channel insertion into the apical membrane of renal tubule cells, producing concentrated urine (Robben et al., 2004). The nonpeptide V2-selective agonist OPC-51803, studied in cells expressing cloned human vasopressin receptor subtypes, offers a pharmacological comparison point for distinguishing V2 from V1a activity at the receptor level (Nakamura et al., 2000). The lysine side chain at position 8 is shorter and less bulky than arginine, and the absence of the guanidinium group likely reduces the interaction geometry with key residues that favor pressor signaling at V1a — a property consistent with the card's documented rationale of "reduced vasopressor activity while retaining antidiuretic signaling."
Evidence
- Human: No human clinical data for (Lys8)-Vasopressin are present in the dossier.
- Animal: Not documented in the available sources.
- In vitro: The 1967 synthesis paper by Zaoral and colleagues reported the preparation of the compound; detailed receptor binding or functional assay data are not captured in the available dossier sources.
Mechanism
The vasopressin receptor family comprises three G-protein-coupled subtypes. V1a (avpr1a) couples to Gq, driving phospholipase C activation and vasoconstriction in smooth muscle. V2 (avpr2) couples to Gs, raising intracellular cAMP via adenylyl cyclase and driving aquaporin-2-mediated water reabsorption in the renal collecting duct — the antidiuretic effect. The position-8 residue in vasopressin-family peptides is a well-documented pharmacological handle: substitutions there reliably shift the V1a/V2 activity ratio. The Möller et al. (2007) study of conopressin variants in the venom of cone snails illustrates how structurally conserved the CYFQNCPKG scaffold is across vertebrates and invertebrates, with position-8 variation — Arg, Lys, Leu, Ile — producing the diverse receptor selectivity profiles seen across species. The Lys8 substitution in this analog removes the arginine guanidinium group, and the resulting change in receptor contact geometry is the presumed basis for the reduced pressor profile noted in the card metadata.
Related peptides
- Vasopressin (arginine vasopressin / AVP) — the parent nine-amino-acid hormone from which (Lys8)-Vasopressin is derived by a single position-8 substitution; the founding member of the vasopressin/oxytocin family.
- Desmopressin — the clinically established V2-selective analog (1-deamino-8-D-Arg vasopressin) engineered by Ferring to eliminate V1a pressor activity; the closest pharmacological comparator in therapeutic use.
- Oxytocin — the nine-amino-acid sister hormone differing from vasopressin at positions 3 and 8; shares the Cys1–Cys6 disulfide ring and C-terminal amide scaffold.
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.
Does the AI binding prediction fail because it models the peptide as a flexible chain rather than the rigid ring it actually forms in biology?
If true, researchers relying on these scores to prioritize vasopressin analogs for development could be misled. Recognizing this gap would prompt better computational tools for cyclic peptide drugs, a class that includes many important hormones and antibiotics.
Can the Lys8 amino acid act as a built-in attachment point for molecular tags that make the drug last much longer in the body?
If confirmed, chemists could attach a fatty acid or polymer to this exact spot to create a once-weekly injection for diabetes insipidus or nighttime fluid disorders, making treatment far more convenient than current daily or multiple-daily doses.
Does the Lys8 change make this peptide stay attached to its kidney receptor for a longer time, even if it does not bind more tightly?
A longer 'grip time' on the kidney receptor could mean longer-lasting water retention from a single dose, which would be valuable for patients who need stable fluid control overnight, such as those with bedwetting or nighttime urination disorders.
Could this peptide influence the body's stress response through the pituitary gland without dangerously raising blood pressure?
If true, this could open a new way to treat stress-related disorders such as PTSD or Cushing's disease, conditions where the body's stress hormone system is overactive, without the blood pressure dangers of natural vasopressin.
Is the molecular 'ring shape' the main reason this peptide binds its receptor, with position 8 only fine-tuning strength?
If the ring structure is what locks the peptide onto the receptor, designers could freely adjust position 8 to tune potency and selectivity without worrying about losing the binding foothold. That insight could accelerate design of safer water-retention drugs.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9494625329971313 | boltz-2 |
| ranking score | 0.7180057764053345 | 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{pep10513,
sequence = {CYFQNCPKG},
target = {avpr1a},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}