Thyroxine-protein interactions: II. The binding of thyroxine and its analogues to human serum albumin

Abstract

The relative affinities of various thyroxine analogues for albumin have been determined. Estimations of relative binding affinities were based on a comparative study of the abilities of the analogues to displace thyroxine from binding sites on albumin. The results indicate that the substituents on thyroxine most directly involved in binding are: (1) the phenolic hydroxyl group; (2) iodine atoms in both the 3′- and 5′-positions of the thyronine molecule; (3) the diphenyl ether group. The absence of any one of these substituents from the molecule leads to an appreciable reduction in relative binding affinity. With regard to the alanine side chain of thyroxine, it appears that neither a free carboxylate ion nor a free α-amino group are required for binding. The results of experiments on the effect of d-thyroxine on the binding of l-thyroxine indicate that binding is not stereospecific. The constants for the binding of tetraiodothyropropionic acid by albumin have been determined.