State-of-the-art photoactivation strategies in chemical biology provide spatiotemporal control and visualization of biological processes. However, using high-energy light (λ < 500 nm) for substrate or photocatalyst sensitization can lead to background activation of photoactive small-molecule probes and reduce its efficacy in complex biological environments. Here we describe the development of targeted aryl azide activation via deep red-light (λ = 660 nm) photoredox catalysis and its use in photocatalysed proximity labelling. We demonstrate that aryl azides are converted to triplet nitrenes via a redox-centric mechanism and show that its spatially localized formation requires both red light and a photocatalyst-targeting modality. This technology was applied in different colon cancer cell systems for targeted protein environment labelling of epithelial cell adhesion molecule (EpCAM). We identified a small subset of proteins with previously known and unknown association to EpCAM, including CDH3, a clinically relevant protein that shares high tumour-selective expression with EpCAM.

化学生物学中最先进的光活化策略提供了生物过程的时空控制和可视化。然而，使用高能光 ( λ < 500 nm) 进行底物或光催化剂敏化可能会导致光活性小分子探针的背景激活，并降低其在复杂生物环境中的功效。在这里，我们描述了通过深红光（ λ = 660 nm）光氧化还原催化靶向芳基叠氮化物活化的发展及其在光催化邻近标记中的应用。我们证明芳基叠氮化物通过氧化还原中心机制转化为三线态氮宾，并表明其空间局部形成需要红光和光催化剂靶向模式。该技术应用于不同结肠癌细胞系统中，对上皮细胞粘附分子（EpCAM）进行靶向蛋白质环境标记。我们鉴定了一小部分与 EpCAM 具有先前已知和未知关联的蛋白质，包括 CDH3，这是一种与 EpCAM 具有高肿瘤选择性表达的临床相关蛋白质。