State Key Laboratory of Analytical Chemistry for Life Sciences, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China.
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, 210023, China.
Angew Chem Int Ed Engl. 2022 Jun 7;61(23):e202200239. doi: 10.1002/anie.202200239. Epub 2022 Apr 5.
The development of new bioorthogonal reactions with mutual orthogonality to classic bioorthogonal reactions such as the strain-promoted azide-alkyne click reaction and the inverse-electron-demand Diels-Alder reaction is of great importance in providing chemical tools for multiplex labelling of live cells. Here we report the first anionic cycloaddend-promoted bioorthogonal cycloaddition reaction between phenanthrene-9,10-dione and furan-2(3H)-one derivatives, where the high polarity of water is exploited to stabilize the highly electron-rich anionic cycloaddend. The reaction is metal- and strain-free, which proceeds rapidly in aqueous solution and on live cells with a second-order rate constant up to 119 M s . The combined utilization of this reaction together with the two other widely used bioorthogonal reactions allows for mutually orthogonal labelling of three types of proteins or three groups of living cells in one batch without cross-talking. Such results highlight the great potential for multiplex labelling of different biomolecules in live cells.
发展与经典生物正交反应（如应变促进的叠氮化物-炔点击反应和逆电子需求 Diels-Alder 反应）具有相互正交性的新型生物正交反应对于提供用于活细胞的多标记的化学工具非常重要。在这里，我们报告了第一个阴离子环加成物促进的生物正交环加成反应，涉及菲-9,10-二酮和呋喃-2(3H)-酮衍生物，其中利用水的高极性来稳定高电子富的阴离子环加成物。该反应无金属和应变，在水溶液中和活细胞中快速进行，二级速率常数高达 119 M s 。该反应与另外两种广泛使用的生物正交反应的联合使用可实现三种类型的蛋白质或三组活细胞在一批中互不干扰的相互正交标记。这些结果突出了在活细胞中对不同生物分子进行多标记的巨大潜力。
