Importance of the third amino acid residue of oxytocin for its action on isolated rat uterus: study of relationship between hormone conformation and activity.
In a continued effort to relate the three-dimensional structure of a peptide hormone to its biological activity, the dose-response relationships of [3-phenylalanine] oxytocin (oxypressin), with an aromatic amino acid residue in position 3, and [3-beta-cyclohexylalanine]oxytocin, with an aliphatic amino acid residue to position 3, were determined in the rat uterine assay in vitro and compared to that of oxytocin. Oxypressin has not only a lower affinity for the smooth muscle receptor than the natural hormone, but also a decreased maximal response (efficacy). [3-beta-Cyclohexylalanine]oxytocin exhibits an even lower affinity than oxypressin, but retains the same maximal response as oxytocin. A reorientation of the tyrosine sidechain, caused by the presence of a neighboring aromatic sidechain in position 3, away from the surface of the 20-membered ring is though to remove the phenolic hydroxyl group from its optimal position in the "active center" of oxytocin and give rise to the reduced efficacy of oxypressin.
D000818:Animals; D001665:Binding Sites; D001681:Biological Assay; D005260:Female; D066298:In Vitro Techniques; D008958:Models, Molecular; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects*
D011956:Receptors, Cell Surface; D010121:Oxytocin