Oxytocin analogs, potency

Lebl et al. (180) combined the Thr and the carba substitutions, synthesizing [Thr, deamino-i-carba]oxytocin and [Thr, deainino-6-carba]oxytocm. Although these analogs had slightly reduced potency at the uterus receptor, they were more selective, having much lower vasopressor activity. 

Table 2.15 Oxytocin (OT) Analogs with Antagonistic Potencies at the Rat Uterus In Vitro...

Once the synthesis of a biologically active peptide is well in hand it becomes possible to explore the role of the individual amino acid constituents in the interaction between the agonist and its receptor. Replacement of one of the residues by a judiciously selected other amino acid provides an analog of the hormone, which can be more active or less potent than the parent compound. From such changes in potency important conclusions can be drawn on the contribution of certain structural features to biological activity. It seems impractical to enumerate the analogs of oxytocin synthesized for such studies. We must limit our account to a few examples and will try, therefore, to describe compounds which provided information transcending the immediate area of oxytocin. 

Upon evaluation for biological activity in several assay systems crystalline deamino-l-seleno-oxytocin was found to be a highly active compound a comparison of its potency values with those for crystalline deamino-oxytocin, evaluated in the same assay systems, reveals that the biological activity spectra of these two analogs differ [Table l]. These differences in activity may be associated with the larger diameter and an increased polarizability of the selenium moiety as compared with the sulfur moiety. 

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