Synthesis and some pharmacological properties of oxytocin and vasopressin analogues with sarcosine or N-methyl-L-alanine in position 7.

Abstract

Eight analogues of oxytocin and arginine-vasopressin were synthesized, in which the proline residue in position 7 was replaced by either sarcosine or N-methylalanine; some of the pharmacological properties of these analogues were evaluated. In peptides containing a beta-mercaptopropionic acid residue in position 1, the additivity of the effects of deletion of the amino group in position 1 and of the above-noted replacements in position 7 on biological properties of these analogues was ascertained. All of the analogues were found to be potent in either antidiuretic or uterine activity and also selective in action. From the point of view of pharmacological properties, substitution of sarcosine in position 7 of oxytocin gave analogues with higher oxytocic and milk-ejecting activities than did the substitution of N-methylalanine. The opposite structure-activity relationship was observed with arginine-vasopressin, where the N-methylalanine-containing analogues were more potent than the sarcosine-containing analogues with respect to pressor activity and also, if not deaminated, with respect to antidiuretic activity.