ABSTRACT
The mechanism of action of steroid hormones involves the binding of the steroid to a receptor protein. Examination of the chemical structures of steroids whose affinity for the progesterone receptor is equal to or higher than that of progesterone itself indicates that extensive structural variation is compatible with high affinity binding. The only structural feature common to all compounds with high affinity for the progesterone receptor is the steroid ring system and 4-en-3-one composition. Crystallographic studies of several synthetic steroids having exceptionally high progesterone receptor affinity revealed the presence of an unusual “inverted” A-ring conformation in which the 2ß hydrogen atom is flipped into an equatorial position rather than the normal axial position. X-ray determinations provide information on the most stable conformation of a molecule. The X-ray results on ground state conformation provide a useful basis for evaluating the accuracy and utility of theoretical energy calculations.
