School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology , Tsinghua University , Beijing 100084 , China.
Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School , Sichuan University , Chengdu 610041 , China.
Bioconjug Chem. 2018 Jul 18;29(7):2287-2295. doi: 10.1021/acs.bioconjchem.8b00283. Epub 2018 Jun 14.
A nature-inspired bioorthogonal reaction has been developed, hinging on an inverse-electron-demand Diels-Alder reaction of tetrazine with β-caryophyllene. Readily accessible from the cheap starting material through a scalable synthesis, the newly developed β-caryophyllene chemical reporter displays appealing reaction kinetics and excellent biocompatibility, which renders it applicable to both in vitro protein labeling and live cell imaging. Moreover, it can be used orthogonally to the strain-promoted alkyne-azide cycloaddition for dual protein labeling. This work not only provides an alternative to the existing bioorthogonal reaction toolbox, but also opens a new avenue to utilize naturally occurring scaffolds as bioorthogonal chemical reporters.
一种受自然启发的生物正交反应已经被开发出来，其关键是四嗪与 β-石竹烯的逆电子需求 Diels-Alder 反应。通过可扩展的合成，β-石竹烯化学报告分子可以从廉价的起始原料中轻易获得，具有吸引人的反应动力学和优异的生物相容性，使其适用于体外蛋白质标记和活细胞成像。此外，它可以与应变促进的炔烃-叠氮化物环加成正交使用，用于双重蛋白质标记。这项工作不仅为现有的生物正交反应工具箱提供了替代方案，还开辟了一条利用天然存在的支架作为生物正交化学报告分子的新途径。
