Interaction Between Thyroid Hormones and Erythrocyte Membranes: Competitive Inhibition of Binding ¹³¹I-L-Triiodothyronine and ¹³¹I-L-Thyroxine by Their Analogs

Abstract

Molecular structural characteristics of thyroid hormones which influence binding to the erythrocyte membranes were investigated by competitive binding experiments. The ability of thyroid hormone analogs to displace ¹³¹I-l-thyroxine and ¹³¹I-1-triiodothyronine from the membranes was considered evidence of their competitive binding. The diphenyl ether linkage (thyronine) was essential as compounds with a single aromatic ring were weakly competitive. The presence of three iodine atoms at 3,5 and 3′ positions on thyronine was optimal for maximal competitive binding. There was weak competitive binding of analogs if chlorine or bromine was substituted for iodine. The alanine side chain was required for optimal binding as N-acetyl-1-thyroxine and various deaminated analogs were poor competitors compared to T₄ and T₃. L-isomers of T₄ and T₃ showed greater competitive binding to erythrocyte membranes than the corresponding d-isomers.