Cyclopropenones for Metabolic Targeting and Sequential Bioorthogonal Labeling
Cyclopropenones for Metabolic Targeting and Sequential Bioorthogonal Labeling
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DOI：
10.1021/jacs.7b03010
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发表时间：
2017-05-31
影响因子：
15
通讯作者：
Prescher, Jennifer A.
中科院分区：
文献类型：
--
作者：
Row, R. David;Shih, Hui-Wen;Prescher, Jennifer A.
环丙烯酮是生物正交化学中有吸引力的基序，由于它们的小尺寸和独特的反应模式。不幸的是，反应最快的环丙烯酮对于常规的细胞内使用来说不够稳定。在这里，我们报告环丙烯酮具有改善的稳定性，保持强大的反应性与生物正交膦。合成了功能化的环丙烯酮，并分析了它们在水介质和细胞环境中的寿命。用一组膦探针进一步处理最稳健的环丙烯酮，并测量反应速率。两个膦支架提供了类似的100倍的速率增强相比，以前报道的试剂。重要的是，稳定的环丙烯酮适合于通过遗传密码扩增的重组蛋白质生产。环丙烯酮连接的产物也适合于无痕施陶丁格连接，为串联标记实验奠定了基础。
Cyclopropenones are attractive motifs for bioorthogonal chemistry, owing to their small size and unique modes of reactivity. Unfortunately, the fastest-reacting cyclopropenones are insufficiently stable for routine intracellular use. Here we report cyclopropenones with improved stability that maintain robust reactivity with bioorthogonal phosphines. Functionalized cyclopropenones were synthesized and their lifetimes in aqueous media and cellular environments were analyzed. The most robust cyclopropenones were further treated with a panel of phosphine probes, and reaction rates were measured. Two of the phosphine scaffolds afforded similar to 100-fold rate enhancements compared to previously reported reagents. Importantly, the stabilized cyclopropenones were suitable for recombinant protein production via genetic code expansion. The products of the cyclopropenone ligation were also amenable to traceless Staudinger ligations, setting the stage for tandem labeling experiments.