Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya, 464-8601 (Japan).
Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya, 464-8602 (Japan).
Angew Chem Int Ed Engl. 2015 Jun 8;54(24):7193-7. doi: 10.1002/anie.201502942. Epub 2015 May 8.
The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting-edge C-H activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm-changing activity along with the components that trigger opposite modes of action. The first period-shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism.
本文描述了哺乳动物生物钟调节剂 KL001 衍生物的合成和功能分析。通过使用前沿的 C-H 活化化学方法，快速构建了 KL001 衍生物的重点文库，从而确定了诱导节律变化活性的 KL001 衍生物的关键部位，以及触发相反作用模式的组成部分。因此，发现了第一批针对隐花色素（CRY）的缩短周期分子。对这些化合物对 CRY 稳定性影响的详细研究表明存在一种尚未发现的调节机制。
