Synthesis and pharmacological properties of [1-L-penicillamine,4-L-leucine]oxytocin.
For the synthesis of [1-L-penicillamine,4-L-leucine]oxytocin (2), Z-Tyr(Bzl)-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with anhydrous HBr, and the resulting partially deprotected octapeptide was coupled with Z-penicillamine(Bzl) in a condensation reaction mediated by dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. The protected nonapeptide Z-penicillamine(Bzl)-Tyr-Ile-Leu-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 was treated with Na in NH3 and the resulting disulfhydryl compound was subjected to oxidative cyclization in H2O-CH3OH with ICH2CH2I, Purification of 2 was effected by partition chromatography and gel filtration. The analog possesses antioxytocic and antiavian vasodepressor pA2 values of 6.77 and 7.21, respectively, and has no antipressor or anti-ADH activity. Its biological activity spectrum is qualitatively identical with that of [1-penicillamine]oxytocin. In contrast to the marked natriuretic-diuretic and anti-antidiuretic activity of [Leu4]oxytocin, 2 exhibits none of these effects on the rat kidney.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002645:Chickens; D003864:Depression, Chemical; D004231:Diuresis / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007930:Leucine / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects
D010121:Oxytocin; D007930:Leucine; D010396:Penicillamine