Thyroactive

This apparent dilema was resolved when further crystallographic data on T3 compounds became available (11,12,13,14,15). (See reference 11 for a detailed list of thyroactive crystal structure studies.) These determinations show the 3 -I in the distal conformation and further showed that either the distal or proximal conformer could be isolated by changing the crystallizing media (13,14). These data prompted further NMR and MQ studies which showed a nearly equal distal/proximal ratio in solution (16) and a much smaller barrier to internal rotation (17). Thus these data have shown that the distal and proximal conformers are readily accessible in solution and that the energy barrier to free rotation is small enough so that the stereospecific conformer required by a receptor is easily accessible. 

Figure 6. Plot of the torsion angle (C5-C4-041-C1 ) and (C4-041-C1 -C6) for those thyroactive crystal structures listed in Ref. 11. Diphenylether conformation for all thyroid hormones.

Figure 11. Superposition of molecular structure of ThA with (a) ThF (b) T P (c) Th and (d) all of them, illustrating binding volume of thyroactive acid metabolites, assuming 4 -phenoxy ring fixed.

In addition, the net charge of the hormone could also influence its binding ability. Thus, the observation of conformational patterns among thyroactive structures which correlate with function, activity and binding data provide useful information in describing specific types of hormone-receptor interactions. 

Pittman CS, Pittman JA, Relation of chemical structure to the action and metabolism of thyroactive substances, in Handbook of Physiology, Greer ME, Solomon DH (eds).. Section 7, volume III, Thyroid, American Physiological Society, Washington, DC, pp 233 (1974)... 

M. C. Cottrell, and S. A. Tepper Oxidation of cholesterol by rat liver mitochondria effect of thyroactive compounds. J. Cell. comp. Physiol. 60, 105 (1962). 

---