Cody V
Science. 1978 Sep 22;201(4361):1131-3. doi: 10.1126/science.684433.
The molecular conformation of the halogen-free thyroxine analog 4-methoxy-3,5,3'-trimethyl-L-thyronine -n-acetyl ethyl ester has been determined by x-ray diffraction techniques. The unsubstituted parent compound, trimethylthyronine, has significant biological activity in rat thymocyte tests when compared with the thyroid hormone 3,5,3'-triiodo-L-thyronine (T3). Although no activity data are available for the analog studied, it is presumed to be inactive because of the 4-methoxy blocking group. The observed conformation of this structure is similar to that found for the natural hormone T(3). The 3'-methyl group is distal, the overall conformation is cisoid, and the diphenyl ether conformation is twist-skewed. The results of this diffraction study show that methyl substituents are capable of maintaining the thyronine conformation required for hormonal activity; they suggest that iodine enhances hormone-protein binding because of the electronic effects it produces either by alteration of molecular charge distributions or by direct charge-transfer interactions with the serum or nuclear binding proteins.
通过X射线衍射技术测定了无卤甲状腺素类似物4-甲氧基-3,5,3'-三甲基-L-甲状腺素-n-乙酰乙酯的分子构象。与甲状腺激素3,5,3'-三碘-L-甲状腺原氨酸（T3）相比，未取代的母体化合物三甲基甲状腺原氨酸在大鼠胸腺细胞试验中具有显著的生物活性。尽管没有所研究类似物的活性数据，但由于4-甲氧基阻断基团，推测其无活性。该结构观察到的构象与天然激素T3的构象相似。3'-甲基基团在远端，整体构象为顺式，二苯醚构象为扭曲倾斜。该衍射研究结果表明，甲基取代基能够维持激素活性所需的甲状腺原氨酸构象；结果表明，碘由于其通过改变分子电荷分布或通过与血清或核结合蛋白的直接电荷转移相互作用而产生的电子效应，增强了激素与蛋白质的结合。
