Conformational studies of steroids: Correlations with biological data

Abstract X-Ray crystal structure analysis provides precise and accurate data concerning steroid structure and conformation. The crystal and molecular structure data of over 200 steroids are being collected and analyzed in the Atlas of Steroid Structure . This extensive analysis plainly shows that crystal packing forces have little influence upon molecular conformation and that the overall conformation of steroids and the orientation of functional groups are clearly controlled by intramolecular forces. The feasibility of specific interactions with protein molecules is in turn dependent upon overall conformation. Information concerning both of these aspects of steroid behavior is provided by crystal structure studies. The details of molecular mechanisms of conformational transmission and the nature of correlations between molecular structure and function can be proposed on the basis of these data. The most active naturally occurring steroids are observed to possess the greatest degree of conformational flexibility. Significantly different conformers of a hormone are probably responsible for different aspects of its action in the biological setting. In synthetic steroidal hormones further substitution on the steroid nucleus generally removes conformational flexibility. The less flexible molecule may now be a better competitor than the natural hormone for one type of protein interaction, but be much less competitive in other protein interactions, as is suggested by the highly specific activity enhancement of synthetic steroidal hormones.