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Article Abstract
G-rich sequences of DNA and RNA can form G-quadruplex (G4) structures, modulating a myriad of biological processes. Thus, it is imperative to understand the structural topologies, location, and function of G4s under cell-free conditions and in the cellular milieu. In the present study, we report three small-molecule fluorescent probes based on azlactones (-) that significantly light up (∼65-135-fold) the parallel topology of the , , and mitochondrial HRCC G4 DNAs. The lead probe AZL1 exhibits a 2:1 binding stoichiometry with G4 DNA by accessing the 5' and 3'-G-quartets. It shows limited cytotoxicity and exhibits fluorescence light-up in the cytoplasm of the HeLa cells due to weak colocalization with the mitochondrial G4 DNAs along with strong colocalization with lipid droplets. These results demonstrate that azlactone-based probes are useful tools to sense G4 structures in a cell-free environment and could be further engineered for potential bioimaging and diagnostic applications.
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