Multimodal bioorthogonal small molecule probes play a pivotal role in drug-focused biomedical research. However, existing drug tracking and imaging techniques face obstacles in living organisms, hindering precise drug localization and target protein capture. Herein, we introduced a multimodal probe naMed. 1-(azidomethyl) pyrene-4,5-dione (AMPD). The probe incorporates adjacent dione structures at the pyrene core. AMPD selectively interacts with oxygen-rich alkene-labeled drug molecules under ice blue LED light exposure, producing specific fluorescence emission and enabling tracking and flow cytometry sorting. A methyl azide group was also introduced at the pyrene core to help efficiently enrich target proteins click chemistry with alkyne-functionalized beads. AMPD demonstrates exceptional biocompatibility, rendering it highly suitable for visual photo-triggered tracking studies. Combined with metabolic labeling using an oxygen-rich alkene-tagged drug molecule probe, AMPD is effective for live animal, tissue, cellular, and in-gel imaging, as well as target protein identification through magnetic capture. With its versatile capabilities, AMPD enhances our comprehension of drug-target interactions at the level and expedites the process of drug discovery.

中文翻译：

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通过视觉代谢标记，利用多模式生物正交 AMPD 探针揭示药物靶点

多模式生物正交小分子探针在以药物为重点的生物医学研究中发挥着关键作用。然而，现有的药物追踪和成像技术在生物体中面临障碍，阻碍了药物的精确定位和目标蛋白捕获。在这里，我们介绍了一种多模态探针 naMed。1-（叠氮基甲基）芘-4,5-二酮（AMPD）。该探针在芘核心处结合了相邻的二酮结构。AMPD 在冰蓝色 LED 光照射下选择性地与富氧烯烃标记的药物分子相互作用，产生特定的荧光发射并实现跟踪和流式细胞术分选。还在芘核心引入了甲基叠氮基团，以帮助使用炔烃功能化珠子有效地丰富目标蛋白点击化学。AMPD 表现出卓越的生物相容性，使其非常适合视觉光触发的跟踪研究。与使用富氧烯烃标记药物分子探针的代谢标记相结合，AMPD 可有效用于活体动物、组织、细胞和凝胶内成像，以及通过磁捕获识别目标蛋白。凭借其多功能功能，AMPD 增强了我们对药物与靶标相互作用水平的理解，并加快了药物发现的过程。