Innes-Gold Sarah, Cheng Hanzeng, Liu Luping, Cohen Adam E
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
ACS Chem Biol. 2025 Feb 21;20(2):455-463. doi: 10.1021/acschembio.4c00756. Epub 2025 Jan 21.
We present versatile tools for intersectional optical and chemical tagging of live cells. Photocaged tetrazines serve as "photo-click" adapters between recognition groups on the cell surface and diverse chemical payloads. We describe two new functionalized photocaged tetrazine structures which add a light-gating step to three common cell-targeting chemical methods: HaloTag/chloroalkane labeling, nonspecific primary amine labeling, and antibody labeling. We demonstrate light-gated versions of these three techniques in live cultured cells. We then explore two applications: monitoring tissue flows on the surface of developing zebrafish embryos, and combinatorial multicolor labeling and sorting of optically defined groups of cells. Photoclick adapters add optical control to cell tagging schemes, with modularity in both tag and cell attachment chemistry.
我们展示了用于活细胞交叉光学和化学标记的多功能工具。光笼化四嗪用作细胞表面识别基团与多种化学负载之间的“光点击”适配器。我们描述了两种新的功能化光笼化四嗪结构，它们为三种常见的细胞靶向化学方法增加了光门控步骤：卤代标签/氯代烷烃标记、非特异性伯胺标记和抗体标记。我们在活培养细胞中展示了这三种技术的光门控版本。然后，我们探索了两种应用：监测发育中的斑马鱼胚胎表面的组织流动，以及对光学定义的细胞群进行组合多色标记和分选。光点击适配器为细胞标记方案增加了光学控制，在标签和细胞附着化学方面都具有模块化。
