Studies on the importance of the asparagine residue in oxytocin. Synthesis and some pharmacological properties of [1-alpha-mercaptoacetic acid, 5-isoasparagine] oxytocin.

[1-Alpha-Mercaptoacetic acid, 5-isoasparagine] oxytocin was synthesized to study the effects of moving the side chain carboxamide group of the amino acid residue in position 5 of oxytocin from the beta to the alpha position. The analog has an isoasparagine residue in position 5 and the 20-membered ring size of oxytocin is maintained by substituting cysteine in position 1 of oxytocin by alpha-mercaptoacetic acid. The analog was found to possess 0.098 +/- 0.002 U/mg of uterotonic activity but no milk-ejecting, antidiuretic or rat pressor activity could be detected. The substance did not inhibit the uterotonic or milk-ejecting activity induced by oxytocin nor the antidiuretic or rat pressor responses to the USP posterior pituitary standard. These results, together with the data available in the literature, indicate that an analog of oxytocin lacking the asparagine residue in position 5 is neither an agonist nor an antagonist. The observations may mean that the asparagine residue is critically important for the interaction of oxytocin with its receptor.