Apparent stereochemical complementarity of estrogens and helical cavities between DNA base pairs: Implications for the mechanism of action of steroids

Abstract

The shape of the space occupied by a model of the estrogenic steroid hormone estradiol-17 beta conforms closely to a helical cavity between neighboring base pairs in partially coiled B-DNA. The orientation of estradiol-17 beta when fitted into DNA allows stereochemically complementary hydrogen bonding of both the 3- and 17 beta-hydroxyl groups to phosphate oxygens of the deoxyribose-phosphate backbone on adjacent strands. Changes in the chirality (handedness) of the steroid skeleton or in the absolute stereochemistry of hydrogen bonding groups prevent formation of complementary fits in the DNA. Synthetic estrogens can also adopt conformations which are stereochemically complementary to the cavities between base pairs. The complementary relationships between active estrogens and nucleic acids may be related to constraints on the evolution of the structure and the biological function of steroids.