Bioorthogonal Cycloadditions with Sub-Millisecond Intermediates
Bioorthogonal Cycloadditions with Sub-Millisecond Intermediates
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DOI：
10.1002/anie.201710262
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发表时间：
2018-01-26
影响因子：
16.6
通讯作者：
Bayley, Hagan
中科院分区：
文献类型：
--
作者：
Qing, Yujia;Pulcu, Goekce Su;Bayley, Hagan
基于四嗪和悉尼酮的点击反应已经成为重要的生物缀合策略，具有快速动力学和N-2或CO2作为唯一的副产物。这些反应的机理研究集中在初始速率决定环加成步骤。随后的N-2或CO2从双环中间体的释放已接近主要通过计算研究，预测飞秒的寿命。在本研究中，涉及N-2或CO2挤出的生物正交环加成反应已经在单分子水平上通过使用蛋白质纳米反应器进行了实验研究。在这种方法的分辨率，反应似乎发生在一个单一的步骤中，这将中间体的寿命上限约为80 μ s，这与计算工作是一致的。
Tetrazine- and sydnone-based click reactions have emerged as important bioconjugation strategies with fast kinetics and N-2 or CO2 as the only byproduct. Mechanistic studies of these reactions have focused on the initial rate-determining cycloaddition steps. The subsequent N-2 or CO2 release from the bicyclic intermediates has been approached mainly through computational studies, which have predicted lifetimes of femtoseconds. In the present study, bioorthogonal cycloadditions involving N-2 or CO2 extrusion have been examined experimentally at the single-molecule level by using a protein nanoreactor. At the resolution of this approach, the reactions appeared to occur in a single step, which places an upper limit on the lifetimes of the intermediates of about 80 mu s, which is consistent with the computational work.