Synthesis and some pharmacological properties of [1-beta-mercapto-beta,beta-diethylpropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin.
The synthesis of the protected polypeptide precursor of [1-beta-mercapto-beta,beta-diethylpropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin was performed in a stepwise manner by solution techniques. This analog of oxytocin has two modifications, each of which taken alone gives analogs which inhibit some of the pharmacological responses to oxytocin. The S-ethylcarbamoyl protecting groups of beta-Mpa(beta-Et2)(Ec)-Dbt-Ile-Gln-Asn-Cys(Ec)-Pro-Leu-Gly-NH2 were removed in refluxing liquid NH3, and the resulting disulfhydryl compound was oxidatively cyclized in H2O-MeOH with ICH2CH2I. Purification was effected by partition chromatography and gel filtration. The analog possesses antioxytocic (pA2 = 7.08) and antiavian vasodepressor (pA2 = 7.38) activities but has neither agonist nor antagonist activity in the rat pressor assay. These potencies are close to those exhibited by [1-beta-mercaptopropionic acid,2-(3,5-dibromo-L-tyrosine)]oxytocin but different from those of [1-beta-mercapto-beta,beta-diethylpropionic acid]oxytocin.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002645:Chickens; D003864:Depression, Chemical; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects
D010121:Oxytocin