Molecular structure of thyroxine analogues. Crystal structure of 3,5,3'-triiodothyroacetic and 3,5,3',5'-tetraoiodothyroacetic acid N-diethanolamine (1:1) complexes.
Crystallographic data demonstrated that conformations of thyroid hormones and their derivatives in which the phenyl rings are either skewed (phi,phi'; +/-90,0 degrees) or twist-skewed (phi,phi'; +/-108, +/-28 degrees) are energetically favored. Acetic acid metabolites are consistently observed in the skewed conformation whereas their parent hormones are observed in the twist-skewed conformation. These preferences are manifestations of long-range conformational transmission and together with plasma protein binding data may indicate a site-specific preference for the skewed vs. twist-skewed conformation. These findings result in part from the crystal structure determinations of the N-diethanolamine (1:1) complexes of the active thyroxine metabolites 3,5,3'-triiodothyroacetic acid (T3AA) and 3,5,3'5'-tetraiodothyroacetic acid (T4AA) which are reported here. The conformation of the 3'-iodine in the hypocholestermic agent T3AA is distal, the biologically preferred conformation, and the overall conformation of T3AA is transoid, while that of T4AA is cisoid.
D055598:Chemical Phenomena; D002621:Chemistry; D007461:Iodoacetates; D008958:Models, Molecular; D008968:Molecular Conformation; D013974:Thyroxine / Q000031:analogs & derivatives*
D007461:Iodoacetates; D013974:Thyroxine