MODEL FOR THYROID HORMONE-RECEPTOR INTERACTIONS

Theoretical electronic structure calculations on the thyroid hormones and analogues, as well as model hormone-receptor interactions, have been carried out. These studies (a) support the concept that the 4ʹ-OH group is a H-bond donor to the in vivo nuclear receptor and suggest that at the receptor this OH group is trans to the 3ʹ (distal) substituent; (b) indicate that there is an important intramolecular interaction between 3ʹ and 4ʹ substituents, and those 3ʹ substituents that most favor both 4ʹ OH orientation trans to the 3ʹ group and a more acidic OH group substantially increase binding and biological activity; and (c) support the concept that there is a direct correlation between the conformational free energy of the aromatic rings and biological activity. © 1979, American Chemical Society. All rights reserved.