[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin, a potent inhibitor of oxytocin.
[1-Beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin was prepared from beta-Mpa(beta-(CH2)5)(Bzl)-Tyr(Bzl)-Ile-Gln-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by removal of the Bzl-protecting groups with Na-NH3 followed by cyclization of the resulting disulfhydryl compound with K3Fe(CN)6.The analog was purified by desalting on Sephadex G-15 in 50% HOAc and gel filtration on Sephadex G-25 and LH-20. The protected intermediate above was synthesized from Z-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwose p-nitrophenyl ester method using Nalpha-Boc protection at the penta-, hexa-, and octapeptide stages. The analog was found to be a potent inhibitor of the oxytocic and avian vasodepressor effects of oxytocin (pA2 values of 7.43 and 8.30, respectively) but was only a weak inhibitor of the rat pressor effect of 8-lysine-vasopressin. The rat antipressor potency of [1-deaminopenicillamine]oxytocin was also determined in this study: pA2 = 6.27. Of the alkyl-substituted 1-position analogs of oxytocin studied so far, [1-beta-mercapto-beta,beta-pentamethylenepropionic acid]oxytocin is the most potent antioxytocic agent.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002645:Chickens; D002855:Chromatography, Thin Layer; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000494:pharmacology; D011422:Propionates / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects
D011422:Propionates; D013438:Sulfhydryl Compounds; D010121:Oxytocin