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The First Peptide Hormone Ever Built in a Flask: Vincent du Vigneaud and Oxytocin
Until 1953, no one had built a peptide hormone from raw chemicals. Hormones were extracted from animal glands in tiny amounts, and nobody could be sure that the structure on paper matched what the gland made. A biochemist at Cornell in New York set out to settle the matter with the smallest hormone he could find: oxytocin.
Key takeaways
- Oxytocin is a peptide of nine amino acids with a ring closed by a disulfide bond between two cysteines.
- Du Vigneaud and his team worked out its structure and then synthesized it in 1953.
- The synthetic peptide matched the natural one in every biological test.
- It was the first peptide hormone to be synthesized, and earned him the 1955 Nobel Prize in Chemistry.
- The achievement proved that structure and activity could be tied together, and led to analogs like desmopressin.
A small hormone with a long reputation
Oxytocin comes from the pituitary gland. Physicians had known since the early 1900s that pituitary extracts could cause uterine contractions and milk release. For decades, that was all anyone knew: an activity in a crude extract. Du Vigneaud, who had spent years on sulfur-containing biological molecules, purified the active material and found that it was a short peptide rich in sulfur. We cover its biology in our oxytocin overview.
Reading the sequence
The structure turned out to be Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly, with the last amino acid amidated. The two cysteines at positions 1 and 6 are joined by a disulfide bond, forming a six-amino-acid ring with a three-amino-acid tail. That layout, a ring plus a tail, is shared with its close relative vasopressin. Both the ring and the amide cap are essential for activity, as described in our cysteine post and our terminal modifications post.
Building it
In the early 1950s there was no automated machine. Du Vigneaud’s group built the peptide by joining protected amino acids one at a time in solution, using a protecting group developed by Max Bergmann and Leonidas Zervas to keep the reactive ends from interfering. At the end, the protecting groups were stripped off with sodium in liquid ammonia, and the two cysteines were oxidized to close the ring.
It was painstaking work, and every step needed careful purification. It was another decade before Bruce Merrifield’s idea made the process far faster, as told in the Merrifield story.
The moment of proof
The crucial test was whether the synthetic peptide behaved exactly like the natural hormone. It did. It stimulated uterine muscle, caused milk ejection and affected blood pressure in the same way and at the same strength as oxytocin extracted from glands. If the structure had been wrong, one of those tests would have failed. The result was the first time that anyone had confirmed a hormone’s structure by building it.
What followed
Du Vigneaud went on to synthesize vasopressin the following year. Their small differences, two amino acids out of nine, explain why the two hormones act so differently. Soon chemists were making analogs, changing one position at a time to see what each did, which led to engineered molecules like those in the desmopressin story and the octreotide story. The Nobel committee honored him in 1955.
What it means for peptide research today
- A structure claim is strongest when a synthetic version matches the natural one.
- Identity is confirmed by independent methods, as in HPLC versus mass spectrometry.
- Ring structures and end caps need special attention in quality testing.
- The same principles guide the lab reports we publish.
The bottom line
Du Vigneaud showed that a peptide hormone is a precise molecule that can be built and checked. Read more of the story of peptide medicine in our history of peptide drugs and see how we document each lot on our lab reports page.
Related reading
- Oxytocin research overview
- The desmopressin story
- History of peptide drugs
- Browse the full Research Library
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For laboratory research use only. Not for human or veterinary use, and not intended to diagnose, treat, cure or prevent any condition. This article is educational and is not medical advice.