Molecular Pharmacology, Vol 3, 248-253, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

2-Isoleucine-oxytocin and Deamino-2-isoleucine-oxytocin: Their Synthesis and Some of Their Pharmacologic Activities

¹ Department of Biochemistry, Cornell University Medical College, New York, New York, 10021

2-Isoleucine-oxytocin, an analog in which the tyrosine residue at position 2 in the hormone has been replaced by an isoleucine residue, and deamino-2-isoleucine-oxytocin, an analog in which a further change has been made by replacing the half-cystine residue at position 1 by a -mercaptopropionic acid residue, have been synthesized and assayed for their biological activities. 2-Isoleucine-oxytocin was found to possess 20 ± 0.5 units/mg of oxytocic activity, 48.3 ± 2.5 units/mg of avian vasodepressor activity, about 0.1 unit/ mg of rat pressor activity, and approximately 50 units/mg of milk-ejecting activity. Deamino-2-isoleucine-oxytocin was found to possess about 22 units/mg of oxytocic activity, 81.2 ± 7.3 units/mg of avian vasodepressor activity, about 0.1 unit/mg of rat pressor activity and approximately 80 units/mg of milk-ejecting activity. These biological activities are considerably greater than would have been expected on the basis of the activities of 2-leucine-oxytocin, which are very low.

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ACKNOWLEDGMENTS The authors are indebted to the following members of this laboratory: Mr. Joseph Albert for the elemental analyses; Mr. Roger Sebbane for the amino acid analyses; and Mrs. Maxine Goldberg, Mrs. Frances Richman, Mrs. Marylin Rippe, Miss Carol Snarski, and Miss Margitta Wahrenberg, under the direction of Dr. W. Y. Chan for the bioassays. This work was supported in part by Grant HE-01675 from the National Heart Institute, United States Public Health Service.