The widespread adoption of the bioorthogonal chemical reporter strategy revolutionized chemical biology. However, its translation to living mammals has been challenging, due to the size/stability properties of the chemical reporter group and/or the reaction kinetics of the labeling step. While developing new bioorthogonal reactions has been the traditional approach to optimizing the bioorthogonal chemical reporter strategy, here we present a different avenue, leveraging intermolecular interactions, to create bioorthogonal host−guest pairs. This approach, deemed "bioorthogonal complexation, does not rely on activated functional groups or second-order rate constants. We utilize the cucurbit[7]uril (CB[7]) scaffold to showcase bioorthogonal complexation and determine that medium-affinity (K_a ≈ 10⁸–10⁹ M^–1) guests efficiently label cell surfaces and outperform the strain-promoted azide-alkyne cycloaddition. Finally, we implement bioorthogonal complexation in the chemical reporter strategy through the metabolic incorporation of ortho-carborane into cell-surface glycans and detection with a CB[7]-fluorescein conjugate.

中文翻译：

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通过生物正交主客体化学进行细胞表面标记

生物正交化学报告策略的广泛采用彻底改变了化学生物学。然而，由于化学报告基团的大小/稳定性和/或标记步骤的反应动力学，将其转化为活的哺乳动物一直具有挑战性。虽然开发新的生物正交反应一直是优化生物正交化学报告策略的传统方法，但在这里我们提出了一种不同的途径，利用分子间相互作用来创建生物正交主客体对。这种被认为是“生物正交络合”的方法不依赖于活化的官能团或二阶速率常数。我们利用葫芦[7]脲 (CB[7]) 支架来展示生物正交络合并确定中等亲和力 ( K _a ≈ 10⁸ –10 ⁹ M ^–1 ) guests 有效地标记细胞表面并优于应变促进的叠氮化物-炔烃环加成。最后，我们通过将邻碳硼烷代谢掺入细胞表面聚糖并使用 CB[7]-荧光素缀合物进行检测，在化学报告策略中实施生物正交络合。