Thyroxine-binding globulin: specificity for the hormonally active conformation of triiodothyronine

The conformational requirements for binding of triiodothyronine to thyroxine-binding globulin were investigated with triiodothyronine analogs having restricted rotation at the ether bond. Although it has been reported that the predominant conformation of triiodothyronine carries the 3' iodine in a position proximal to the phenylalanine ring, the analog for the distal, hormonally active orientation of the 3' iodine is more effective in displacing triiodothyronine and thyroxine from thyroxine-binding globulin. The lower binding affinity of thyroxine-binding globulin for triiodothyronine as compared to thyroxine may be explained by specificity of the binding site for the less abundant conformation of triiodothyronine.