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 ∼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.

中文翻译：

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用于代谢物靶向和顺序生物正交标记的环丙烯酮

环丙烯酮由于尺寸小和独特的反应方式，因此是生物正交化学的诱人基序。不幸的是，反应最快的环丙烯酮对于常规的细胞内使用而言不够稳定。在这里，我们报告具有改善的稳定性的环丙烯酮，与生物正交膦保持稳定的反应性。合成了功能化的环丙烯酮，并分析了它们在水性介质和细胞环境中的寿命。用一组膦探针进一步处理最坚固的环丙烯酮，并测量反应速率。与以前报道的试剂相比，两种膦骨架提供了约100倍的速率增强。重要的是，稳定化的环丙烯酮适合通过遗传密码扩展生产重组蛋白。