Studies of Relationships between Structure and Biological Activity

4 Studies of Relationships between Structure and Biological Activity 

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. 

At this point it might be appropriate to mention that it was not fully justified to attribute a direct biological role to the disulfide. The biological activity of reduced oxytocin is obviously due to reoxidation in the blood or in the target tissues. When the experiments with the reduced form (oxytocein) were carried out 

The analogs discussed so far reveal certain features of the various oxytocin receptors. The molecule binds, however, not merely to the receptors in the target organs, but also to a carrier protein, originally known as the van Dyke protein [54] that was renamed neurophysin after its isolation in pure form. It is rather remarkable that for binding of oxytocin to this protein the free N-terminal amino group, which is not needed for activity, is quite essential [55]. 

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