Lysine-vasotocin, a synthetic analogue of the posterior pituitary hormones containing the ring of oxytocin and the side chain of lysine-vasopressin.

The synthesis of oxytocin (I), arginine-vasopressin (2)) and lysine-vasopressin (3-5) has opened the way for the synthesis of analogues of the natural hormones, thus affording an opportunity to study the relationship between structure and biological activity in these hormones. One of the most interesting analogues thus far prepared is arginine-vasotocin, an octapeptide amide containing the ring of oxytocin and the side chain of arginine-vasopressin. Some time after the synthesis of this substance and the investigation of some of its biological effects in this laboratory (6), the arginine-vasotocin was tentatively identified as a naturally occurring hormone in fowl neurohypophysial extracts by Munsick, Sawyer, and van Dyke (7-9) on the basis of pharmacological and chromatographic evidence. Chauvet, Lenci, and Acher (10) in a preliminary communication have reported the isolation of a peptide from fowl neurohypophysial extracts which appears to be arginine-vasotocin. Thus the evidence is convincing at the present time for the occurrence in nature of arginine-vasotocin. If further work substantiates this conclusion, the synthesis of this compound would represent a remarkable example of the synthesis of a polypeptide hormone before its identification as a natural product. Sawyer, Munsick, and van Dyke (8) have also studied neurohypophysial extracts from cold-blooded vertebrates and have advanced the hypothesis that arginine-vasotocin occurs not only in birds but also in reptiles, amphibians, and teleosts. Their evidence also indicates that it appears in the most primitive living vertebrates, the cyclostomes. The one elasmobranch (spiny dogfish) that they studied appeared to possess an active peptide unlike any that they had encountered elsewhere among the vertebrates. Pharmacological studies on the pituitaries of fish, fowl, and frogs by Pickering and Heller (11) also provided evidence for the presence of a peptide different from arginineor lysine-vasopressin in these species. Maetz et ~2. (12, 13) came to a similar conclusion with regard to cold-blooded vertebrates. More recently Acher et al. (14) isolated a substance from frog posterior pituitaries with a composition corresponding to that of arginine-vasotocin. Furthermore, the biological properties of the isolated product corresponded to those of synthetic arginine-vasotocin furnished to these investigators by our laboratory. The present paper describes the synthesis and pharmacological properties of Zysine-vasotocin, a compound similar to arginine-vasotocin but having the ring of oxytocin attached to the