title: N-Acetyl-[2-(O-methyl)tyrosine]arginine-vasopressin, an interesting antagonist of the vasopressor response to vasopressin.
abstract: The synthesis of N-acetyl-[2-(O-methyl)tyrosine]arginine-vasopressin [Ac-Tyr(Me)AVP] was undertaken utilizing a combination of the stepwise active ester and fragment condensation methods. Ac-Tyr(Me)AVP is an antagonist of the vasopressor response to vasopressin (pA2 = 7.18 +/- 0.08), devoid of vasopressor agonist activity, and has an antidiuretic potency of 0.026 +/- 0.002 unit/mg, a 15 000-fold decrease over the antidiuretic activity of [2-(O-methyl)tyrosine]arginine-vasopressin. The analogue is also an antagonist of the in vitro uterotonic activity of oxytocin with pA2 values of 7.29 +/- 0.08 in the absence of Mg2+ and 6.73 +/- 0.14 in 0.5 mM Mg2+. This result of Nalpha-acetylation of Tyr(Me)AVP parallels similar results in the oxytocin series and suggests that this substitution should be considered in the design of potential antagonists of the antidiuretic response to vasopressin.
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects; D014667:Vasopressins / Q000037:antagonists & inhibitors*
chemical_list: D014667:Vasopressins; D001127:Arginine Vasopressin; C025937:vasopressin, N-acetyl-O-methyl-Tyr(2)-Arg(8)-