Synthetic I-N-Carbamylhemicystine-2-O-methyltyrosine-oxytocin (N-Carbamyl-O-methyl-oxytocin): a Specific Antagonist to the Actions of Oxytocin and Vasopressin on the Uterus and Mammary Gland

Abstract

CYANATE reacts with the terminal amino groups of proteins and peptides to form N-carbamyl derivatives¹. Bisset, Poisner and Smyth² tested the biological activity of oxytocin which had been carbamylated by reaction with cyanate. The products of the reaction specifically inhibited the response of the isolated rat uterus, rat blood pressure and chicken blood pressure to oxytocin but had a weak stimulant action, like that of oxytocin itself, on the rat uterus in situ and on the guinea-pig mammary gland, both isolated and in situ. At the time, these effects were attributed to the formation of 1-N-carbamyl-oxytocin³. In later work, however, Smyth⁴ showed that the inhibitory properties were caused by the presence in the reaction mixture of a trace of a dicarbamyl derivative of oxytocin, N-carbamyl-O-carbamyl-oxytocin, in which not only the terminal amino (NH₂) group of the hemicystine residue but also the phenolic hydroxyl (OH) group of the tyrosine residue had undergone carbamylation, and he went on to describe the preparation of a series of stable, doubly modified analogues which were specific antagonists of oxytocin without intrinsic activity on the isolated uterus^4,5. 1-N-Carbamyl-oxytocin, in contrast, was shown to be a weak agonist with no inhibitory action⁴.