Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Department of Chemistry, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China.
Org Lett. 2020 Apr 17;22(8):2920-2924. doi: 10.1021/acs.orglett.0c00578. Epub 2020 Apr 7.
We report here a deep mechanistic study of the "click" -quinone methide (QM) cycloaddition between -quinolinone quinone methide (QQM) and thio-vinyl ether (TV), named as TQ-ligation. DFT calculations revealed the unexpected fact that dehydration of QQM precursors is the rate-determining step of this transformation, and two highly reactive QQM precursors were predicted. Guided by the calculations, a new "click" QM cycloaddition which shows significantly improved kinetics and remarkable efficiency on protein labeling was developed.
我们在此报告了一种深入的机械研究，涉及β-喹啉酮醌甲醚（QQM）与硫代乙烯基醚（TV）之间的“点击” -醌甲醚（QM）环加成反应，称为 TQ 连接。DFT 计算揭示了一个意外的事实，即 QQM 前体的脱水是这种转化的速率决定步骤，并且预测了两种高反应性的 QQM 前体。受计算的指导，开发了一种新的“点击”QM 环加成反应，该反应在蛋白质标记方面表现出明显改善的动力学和显著的效率。
