Peptide hormones generally produce their biological effects by interaction with membrane bound receptors, but we know little about the specific chemical and physical properties of these binding sites. Ultimately hormone-receptor interactions are three dimensional in nature, in which two complementary topological surfaces interact to produce a biological response. These three dimensional features often can be examined by conformational restriction of the peptide hormones. Virtually all peptide hormones have multiple receptors of physiological and pharmacological importance and there is overwhelming evidence that generally each of these receptors utilizes different structural and conformational properties of the hormone. In addition to being the first peptide hormone, whose structure was elucidated and then prepared by total synthesis, oxytocin (OT) was also the first peptide hormone, for which a conformation-biological activity model was proposed. Examination of the possible conformational features of arginine vasopressin (AVP) led researcher to propose a “biologically active conformation” for vasopressin at the kidney anti-diuretic receptor. Structure–activity relationships of leutienizing hormone releasing hormone (LHRH) have been examined by determining the effects of systematic modification of each residue on biological activity. Development of rational approaches to the design of peptide hormone analogs with useful biological and physical properties is still in its infancy. Yet, conformational and topological considerations already have provided new insights into the chemical–physical basis for the biological activity of these compounds.
ASJC Scopus subject areas
- Organic Chemistry