Biochemistry of Amino Acids - A. Meister 1961

Natural Amino Acids
Peptides and Related Compounds
Posterior Pituitary Hormones

Crude preparations of Vasopressin and Oxytocin have been available for A number of years, but the structures of these Hormones have been elucidated only very recently. Du Vigneaud et al. [400–402, 579] determined the structures of oxytocin and vasopressin and achieved the Chemical synthesis of oxytocin. The synthetically produced oxytocin is completely identical to the purified natural product. This is a remarkable achievement, as it marked the first time that a chemical synthesis was accomplished

of a natural polypeptide hormone. Even before the synthesis of oxytocin was realized, du Vigneaud and his coworkers proposed the following structural formula for bovine oxytocin:

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The same Structure was proposed by Tuppy [403, 404], based on data from du Vigneaud and his coworkers, as well as on his own findings obtained using Sanger's METHOD FOR DETERMINING end groups as dinitrophenyl derivatives (p. 35).

Oxytocin was synthesized by the Condensation of N-carbobenzoxy-S-benzyl-L-cysteinyl-L-Tyrosine with L-isoleucyl-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycinamide. The resulting nonapeptide amide was treated with sodium in liquid ammonia to remove the protecting groups, and then oxidized to yield oxytocin.

Bovine vasopressin has a similar structure:

A paper describing the synthesis of porcine vasopressin has recently emerged from du Vigneaud's laboratory [580]. It is noteworthy that the C-terminal residue in the molecules of the aforementioned hormones is glycinamide. This raises an important question: do similar linkages exist in Proteins as well? In the porcine vasopressin molecule, the Arginine residue is replaced by Lysine. Despite this species difference, both vasopressins exhibit nearly identical physiological activity. Oxytocin is one of the principal Hormones of the posterior Pituitary Gland; it stimulates uterine smooth Muscle contraction and milk ejection. Vasopressin raises Blood pressure due to its vasoconstrictive action and also exerts an antidiuretic effect. The structural similarity between vasopressin and oxytocin molecules helps explain the weak oxytocic activity observed in vasopressin preparations and, conversely, perhaps the weak pressor activity found in oxytocin preparations.

These significant breakthroughs in organic synthesis have made it possible to synthesize several compounds structurally related to vasopressin and oxytocin, and to investigate the physiological Properties of the resulting products; ongoing work in this direction will bring us closer to elucidating the MECHANISM OF ACTION of these hormones.