Abstract
Analogues of oxytocin and deamino-oxytocin ([1-β9-mercaptopropionic acid]-oxytocin) with an N4-methyl-L-asparagine residue in place of the glutamine residue in position 4 have been prepared and tested for their biological activities. [4-N4-Methyl-L-asparagine]-oxytocin was found to possess 119 ± 5 units/mg of avian vasodepressor activity, 41 ± 2 units/ mg of rat oxytocic activity, less than 0.5 unit/mg of rat pressor activity, and approximately 0.045 unit/mg of rat antidiuretic activity. The hydro-osmotic activity of the analogue was 2.23 ± 0.40% of that of crystalline deamino-oxytocin upon assay in the toad bladder system. The corresponding activity values for [1-β-mercaptopropionic acid,4-N4-methyl-L-asparagine]-oxytocin were 186 ± 4 units/mg, 59 ± 2 units/mg, less than 0.4 unit/mg, approximately 0.012 unit/mg, and 1.17 ± 0.11%, respectively. Most significantly, the replacement of the N-terminal amino group in [4-N4-methyl-L-asparagine]-oxytocin by hydrogen elicited not only a quantitative but even a qualitative alteration in the hydroosmotic activity.
ACKNOWLEDGMENTS The authors are indebted to the following members of this laboratory: Mr. L. Trauth for synthetic assistance; Mr. D. Schlesinger for amino acid analyses; and Miss M. Wahrenburg, Mrs. B. Dubois, Miss I. Bergman, Miss P. Walter, Mr. V. Sapirstein, and Mr. R. Felson for bioassays.
- Copyright ©, 1969, by Academic Press Inc.
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