THEME:
Nobel LaureatesUnderneath the brain, there is a small, well-protected gland, the pituitary gland. In man it is about as big as a bean. There are secreted several hormones, that is, substances which regulate important physiological functions. spite of its small size, the pituitary gland is made up of several distinct parts with different functions. We are interested here in the posterior lobe, which contains two substances called oxytocin and vasopressin. The former stimulates the contractions of the uterus and also the lactation, the latter raises the blood pressure and regulates the function of the kidneys. As early as in 1933, when rather impure preparations from the posterior lobe were used in experiments, du Vigneaud found a high percentage of sulphur, which seemed to be correlated to the physiological activity.
Using the experimental methods, which the development of science has put at his disposal and making the best of his own intimate knowledge of the organic chemistry of sulphur, du Vigneaud has step by step forced his way. Both hormones were isolated in a state of purity, and it was found that they are built up from amino acids in the same way as proteins, but with a far lower molecular weight. Such compounds are, as distinguished from real proteins, called polypeptides. The nature of the amino acids and their positions in the molecule could be determined. The sulphur is present in cystine. The two hormones have a very similar structure; both contain eight amino acids, connected to a chain, which at one point is closed to a ring. The molecule has some resemblance to a figure six or nine, where the loop contains five amino acids and the “tail” three. Two sulphur atoms, linked to each other, form a part of the ring.
The design of the molecule was thus known. It remained to build it up by synthesis and check the correctness of the design. That was perhaps the most difficult part of the work. The interest was first concentrated on the synthesis of oxytocin. Step by step the amino-acid chain was built up with the two sulphur atoms in the proper positions, one at the end of the chain and the other near the middle. At last the ring was closed by formation of a bond between the sulphur atoms. Now followed the most thrilling moment, the testing of the chemical properties and the physiological activity; perhaps there had been some mistake after all. It turned out, however, that the synthetic polypeptide was identical with the natural product.
