| Abstrakt: |
Two analogues of oxytocin in which the glutamine residue at position 4 has been replaced by isoleucine and leucine residues, respectively, have been prepared by total synthesis via the stepwise p-nitrophenyl ester method. The [4-isoleucine]-oxytocin and [4-leucine]-oxytocin were tested for a number of biological activities, [4-Isoleucine]-oxytocin possesses about 16% of the avian vasodepressor, 7% of the oxytocic, and 45% of the milk-ejecting activities of oxytocin. This analogue possesses negligible pressor and antidiuretic activities. [4-Leucine]-oxytocin possesses approximately 9% of the avian vasodepressor, 2.5% of the oxytocic, and 16% of the milk-ejecting activities of oxytocin. This analogue has no antidiuretic activity. It has a weak and inconsistent depressor effect on the blood pressure. [4-Isoleucine]-oxytocin and [4-leucine]-oxytocin are both considerably less potent than [4-valine]-oxytocin with respect to their avian vasodepressor, oxytocic, and milk-ejecting activities. Of particular interest is the fact that [4-leucine]-oxytocin exhibits in the rat a potent diuretic and natriuretic effect. Futhermore, it inhibits the antidiuretic activity of arginine-vasopressin. |
