Fluorogenic “Photoclick” Labeling and Imaging of DNA with Coumarin-Fused Tetrazole in Vivo

Photoclickable fluorogenic probes will enable visualization of specific biomolecules with precise spatiotemporal control in their native environment. However, the fluorogenic tagging of DNA with current photocontrolled clickable probes is still challenging. Herein, we demonstrated the fast (19.5 ± 2.5 M–1 s–1) fluorogenic labeling and imaging of DNA in vitro and in vivo with rationally designed coumarin-fused tetrazoles under UV LED photoirradiation. With a water-soluble, nuclear-specific coumarin-fused tetrazole (CTz-SO3), the metabolically synthesized DNA in cultured cells was effectively labeled and visualized, without fixation, via “photoclick” reaction. Moreover, the photoclickable CTz-SO3 enabled real-time, spatially controlled imaging of DNA in live zebrafish.