Oxytocin is a peptide. PubChem lists it as a cyclic nonapeptide, CID 439302, CAS 50-56-6, molecular formula C43H66N12O12S2, average molecular weight 1007.2 Da and monoisotopic mass 1006.43646 Da. Its nine residues read CYIQNCPLG, closed by a disulfide bridge between the cysteines at positions 1 and 6 and capped by a C-terminal glycine amide. It differs from vasopressin at exactly two of those nine positions, 3 and 8.

What are oxytocin's identity numbers?

PubChem's ChEBI-sourced description calls oxytocin "a cyclic nonapeptide hormone with amino acid sequence CYIQNCPLG" and "a heterodetic cyclic peptide", meaning a ring closed by something other than a peptide bond, here the sulfur to sulfur link.

The formula and average mass also appear in the FDA-approved label for Pitocin, published on DailyMed:

Pitocin has the empirical formula C 43 H 66 N 12 O 12 S 2 (molecular weight 1007.19).DailyMed structured product label for Pitocin, setid 6e5a66fc

The ring and the amide

UniProt entry P01178 annotates residues 20 to 28 of the oxytocin-neurophysin 1 prepropeptide as the mature peptide, and those nine positions read C, Y, I, Q, N, C, P, L, G. Two further feature lines define everything else: a disulfide joining precursor residues 20 and 25, which are positions 1 and 6 of the mature peptide, and a modified-residue annotation on residue 28, position 9, reading simply "Glycine amide". Wiśniewski and colleagues, in Biopolymers in 2013, describe "a cyclic nonapeptide containing one internal disulfide bond between its Cys(1) and Cys(6) residues".

The one-letter code and notations like -NH2 are explained in how to read a peptide sequence. CYIQNCPLG alone is an incomplete identity: without the ring and the amide it describes a different compound.

Why does one source say nonapeptide and another say octapeptide?

PubChem, ChEBI and UniProt describe nine residues. Du Vigneaud's 1953 synthesis communication and the current Pitocin label say eight. The JACS title reads "THE SYNTHESIS OF AN OCTAPEPTIDE AMIDE WITH THE HORMONAL ACTIVITY OF OXYTOCIN", and the label states:

These properties are thought to be due to the fact that oxytocin and vasopressin differ in regard to only two of the eight amino acidsDailyMed structured product label for Pitocin

Both counts are defensible, because the disagreement is about counting rather than chemistry. The older convention counts the disulfide-linked pair of cysteines once, as the single amino acid cystine, leaving eight units plus the terminal amide. The modern database convention counts residues along the sequence, which gives nine. A source that says eight may simply be quoting a label FDA still maintains.

How does oxytocin differ from vasopressin?

The sequences come from the two UniProt entries, P01178 and P01185, residues 20 to 28 of each precursor. The substitutions are isoleucine to phenylalanine at position 3 and leucine to arginine at position 8, which is what NCBI's scope note says: "It differs from VASOPRESSIN by two amino acids at residues 3 and 8." Everything else is shared: the disulfide between positions 1 and 6, the glycine amide at position 9, the nine-residue length.

In composition the swap adds three carbons and three nitrogens and removes one hydrogen. The mass gap is 77.00 Da monoisotopic, 1083.43785 minus 1006.43646, an unambiguous separation for any instrument that can weigh a peptide.

Three documented reasons the two get confused

An approved label says so, and counts differently. The Pitocin sentence quoted above states the similarity while using the eight-residue convention.

Manufacturing history. The same label says why modern material is made rather than extracted:

The hormone is prepared synthetically to avoid possible contamination with vasopressin (ADH) and other small polypeptides with biologic activity.DailyMed structured product label for Pitocin

Pituitary-extract oxytocin genuinely did carry vasopressin, so the separation problem is documented history.

One receptor family, and one chromosome. NCBI's RefSeq summary for the human AVPR2 gene puts the V2, V1a and V1b vasopressin receptors and the oxytocin receptor in one conserved subfamily, and ends: "All bind similar cyclic nonapeptide hormones." The receptor genes sit on four chromosomes, OXTR on 3, AVPR1A on 12, AVPR1B on 1, AVPR2 on X. The two ligand genes sit together: OXT and AVP are both on chromosome 20, as a gene duplication would predict.

du Vigneaud, 1953 and the 1955 Nobel Prize

The structure proposal appeared in the Journal of Biological Chemistry in December 1953, by du Vigneaud, Ressler and Trippett. The synthesis followed the same year in the Journal of the American Chemical Society, volume 75, issue 19, pages 4879 to 4880, then the full paper, "The Synthesis of Oxytocin", in 1954. The vasopressin structure paper from the same laboratory ran on pages 4880 to 4881 of that issue: the two structures were solved back to back, which is part of why they remain twinned in the literature.

The Nobel Prize in Chemistry 1955 went to Vincent du Vigneaud alone, a 1/1 share, "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone". The Nobel Foundation's facts page, which places him at Cornell University at the time of the award, notes that oxytocin "became the first peptide hormone to have its sequence of amino acids determined".

What the ring and the amide mean for identity work

The C-terminal amide is not decoration. Replace it with a free acid and you get C43H65N11O13S2, average mass 1008.2 Da and monoisotopic 1007.42047 Da, a difference of +0.98402 Da, because one nitrogen plus one hydrogen is exchanged for one oxygen.

That number does a lot of work. Hawe and colleagues, in Pharmaceutical Research in 2009, identified deamidation at Gln4, Asn5 and the C-terminal Gly9 amide under acidic conditions. Each event shifts the monoisotopic mass by the same +0.984 Da.

A mass measurement confirms elemental composition. It does not place the disulfide or order the residues. What a mass match proves, and what it cannot see, is covered in mass spectrometry identity.

Oxytocin appears in our catalog as oxytocin liquid spray, a 10 mL solution in the Liquid sprays category, labelled research use only. Its US regulatory position is set out in the oxytocin nasal spray approval history.

Sources

• PubChem compound record, oxytocin, CID 439302: formula, molecular weight, monoisotopic mass, InChIKey
• PubChem record description for CID 439302, ChEBI and DrugBank sourced
• UniProt P01178, oxytocin-neurophysin 1 prepropeptide, human
• UniProt P01185, vasopressin-neurophysin 2-copeptin, human
• DailyMed, Pitocin (oxytocin injection, USP) structured product label
• Wiśniewski K et al., On the mechanism of degradation of oxytocin and its analogues in aqueous solution, Biopolymers 2013
• Hawe A et al., Towards heat-stable oxytocin formulations, Pharmaceutical Research 2009
• du Vigneaud V et al., The synthesis of an octapeptide amide with the hormonal activity of oxytocin, JACS 1953
• du Vigneaud V et al., The Synthesis of Oxytocin, JACS 1954
• Nobel Prize in Chemistry 1955, Vincent du Vigneaud, facts page, Nobel Foundation
• NCBI Gene AVPR2, GeneID 554, RefSeq summary
• NCBI Gene OXT, GeneID 5020, oxytocin/neurophysin I prepropeptide