A model for thyroid hormone-receptor interactions

Abstract

Theoretical electronic structure calculations on the thyroid hormones [thyroxine, triiodothyronine] and analog, as well as model hormone-receptor interactions, were carried out. The 4''-OH group is evidently a H-bond donor to the in vivo nuclear receptor and at the receptor this OH group is trans to the 3'' (distal) substituent; there is an important intramolecular interaction between 3'' and 4'' substituents and those 3'' substituents that most favor both 4'' OH orientation trans to the 3'' group and a more acidic OH group substantially increase binding and biological activity; there is a direct correlation between the conformational free energy of the aromatic rings and biological activity.