Synthesis and properties of angiotonin.

ANGIOTONIN (hypertensin) was discovered in 1939, but it was not until 1956 that its structure was reported. In 1954 we published an amino acid analysis and a determination of the end amino acids of angiotonin. We know now that the preparation used was about 75 per cent pure, which accounts for the additional amino acids reported; the end amino acids were later shown to be correct. During the purification of hog angiotonin, it was assayed on two separate preparations. One of these, the intact animal measured pressor activity only; the other, the rat's uterus, measured oxytocic activity. In figure 1 is shown what we thought to be two separate factors, a pressor and an oxytocic-pressor substance. The material shown by the large peak has predominantly pressor activity with very little ability to stimulate smooth muscle. The second peak indicates a substance with high oxytocic and high pressor activity. In several preparations we have noted a third pressor substance, but always in small amounts. Numerous angiotonins are possible in a preparation made from proteolytic enzymes. In figure 2 is shown the structure of angiotonin. The complete structure of the decapeptide isolated from beef as first demonstrated by Elliott and Peart' has isoleueine replaced by valine. The structures of horse decapeptide2 and hog angiotonin determined in our laboratory are identical and are shown in this figure. The structure of angiotonin octapep-