Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore-560012 (India).
Angew Chem Int Ed Engl. 2015 Jun 22;54(26):7674-8. doi: 10.1002/anie.201502762. Epub 2015 May 12.
Iodothyronine deiodinases are selenoenzymes which regulate the thyroid hormone homeostasis by catalyzing the regioselective deiodination of thyroxine (T4). Synthetic deiodinase mimetics are important not only to understand the mechanism of enzyme catalysis, but also to develop therapeutic agents as abnormal thyroid hormone levels have implications in different diseases, such as hypoxia, myocardial infarction, critical illness, neuronal ischemia, tissue injury, and cancer. Described herein is that the replacement of sulfur/selenium atoms in a series of deiodinase mimetics by tellurium remarkably alters the reactivity as well as regioselectivity toward T4. The tellurium compounds reported in this paper represent the first examples of deiodinase mimetics which mediate sequential deiodination of T4 to produce all the hormone derivatives including T0 under physiologically relevant conditions.
碘甲状腺原氨酸脱碘酶是一类含硒酶，通过催化甲状腺素（T4）的区域选择性脱碘来调节甲状腺激素的动态平衡。脱碘酶模拟物不仅对于理解酶催化机制非常重要，而且对于开发治疗药物也很重要，因为异常的甲状腺激素水平与多种疾病有关，如缺氧、心肌梗死、危重病、神经元缺血、组织损伤和癌症。本文描述了一系列脱碘酶模拟物中硫/硒原子被碲取代后，其对 T4 的反应性和区域选择性发生了显著变化。本文报道的碲化合物代表了首例介导 T4 连续脱碘生成包括 T0 在内的所有激素衍生物的脱碘酶模拟物。
