β-Carboline-Based Fluorescent Probes Sense and Stabilize G-quadruplex DNA Structures.

DNA forms four-stranded G-quadruplex (G4) structures in guanine-rich regions of the genome, regulating various biological functions, including stalling replication and modulating gene expression at both transcription and translation levels. Thus, investigating the folding, dynamics, and subcellular localization of G4s using small-molecule probes is useful to understand their biological functions. In this study, we report a series of fluorescent probes based on β-carboline that emit upon binding to G4 DNA structures. The lead probe BCC exhibits up to an ∼18-fold fluorescence enhancement (40% quantum yield), 22 °C stabilization, and a binding constant in the range of (0.16-1.3) × 106 M-1 with G4 DNAs. BCC binds G4 structures by accessing the 5'-quartet in a 1:1 binding stoichiometry. It exhibits a bright red fluorescence signal in the nucleoli and cytoplasm of HeLa cells, corresponding to the interaction of the probe with rDNA and mitochondrial DNA, respectively. Overall, these results show that β-carboline probes can be harnessed for sensing and various applications utilizing G4-mediated biological processes.