Synthesis and Some Pharmacological Properties of a Peptide Derivative of Oxytocin

Abstract

Summary

1) The protected decapeptide carbobenzoxyglycyl - S - benzyl - l - cys-teinyl - l - tyrosyl - l - isoleucyl - l - gluta-minyl - l - asparaginyl - S - benzyl - l - cysteinyl - l - prolyl - l - leucylglycinamide was synthesized by coupling of the p-nitrophenyl ester of carbobenzoxyglycine with S-benzyl-l - cysteinyl - l - tyrosyl - l - isoleucyl - l -glutaminyl - l - asparaginyl - S - benzyl - l -cysteinyl - l - prolyl - l - leucylglycinamide. Removal of the protecting groups followed by oxidation to the disulfide gave glycyloxytocin which was isolated by countercurrent distribution. 2) The pharmacological effects of this peptide derivative of oxytocin were investigated by testing it for avian depressor, pressor, and rat uterine-contracting activities. The sample of glycyloxytocin possessed only a slight degree of these 3 activities. It was found to exert a marked inhibitory effect on the avian depressor activity of oxytocin. On the other hand, the glycyloxytocin did not show inhibitory action against oxytocin on the isolated rat uterus or against oxytocin or vasopressin in the assay for pressor activity in the rat. 3) Thus, the attachment of a glycyl residue to the free amino group of oxytocin causes almost complete loss of its avian depressor, rat uterine-contracting, and pressor effects. In addition, it is of considerable interest that this peptide derivative of oxytocin exerts a marked inhibitory action upon the avian depressor effect of the hormone.