Oxytocin

Oxytocin is a nine-residue cyclic peptide: a twenty-membered ring closed by a single disulfide, with a three-residue tail ending in a C-terminal amide. It is the smallest disulfide-constrained molecule in this catalogue.

The sequence is Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly with the C-terminal glycine amidated. Both structural features are recorded independently by two registries: UniProt P01178 annotates a disulfide between precursor residues 20 and 25, which are residues 1 and 6 of the nonapeptide, and a glycine amide at residue 9, while FDA GSRS records the same bridge and the same glycinamide conversion. There is no acetylation and no non-standard residue.

The single disulfide is the entire conformational constraint. Reducing it leaves a floppy linear nonapeptide about two daltons heavier, which is a useful marker in a reduction check. Pro7 sits at the hinge between the ring and the acyclic tail and restricts how that tail can move.

The molecule carries one tyrosine, at position 2, and no tryptophan or phenylalanine. That single aromatic residue plus the cystine makes absorbance at 280 nm workable but weak, and Tyr2 also provides the intrinsic fluorescence that Hawe and colleagues used as a stability readout. There is no methionine; the two cysteines are consumed by the disulfide, so exchange rather than free-thiol oxidation is the relevant chemistry.

Tyr2 does more than absorb light. In the copper complex characterised by Alshanski and colleagues in 2021 by paramagnetic relaxation enhancement NMR, the N-terminal amine is required for binding and the tyrosine ring then forms a cation-pi interaction with the metal.

Its receptor is OXTR (UniProt P30559), a class A G-protein-coupled receptor, resolved by X-ray at 3.2 Angstrom as PDB 6TPK and by cryo-electron microscopy at 2.9 Angstrom bound to a heterotrimeric G protein as PDB 7RYC. Binding to the three vasopressin receptors AVPR1A, AVPR1B and AVPR2 (UniProt P37288, P47901 and P30518) is documented rather than incidental, and UniProt's own mutagenesis annotation quantifies how a single substitution separates them.

Two masses circulate for this compound and they describe different materials. The figure above is the free peptide. The one-to-one acetate salt, registered separately under CAS 6233-83-6, is sixty daltons heavier because it carries one molecule of acetic acid. FDA GSRS also publishes a molecular-formula text field for both forms that is chemically impossible, so the formula above is taken from PubChem CID 439302 instead.