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

Area of Science:

• Biochemistry and Molecular Biology
• Chemical Biology
• Genomics

Background:

• DNA G-quadruplexes (G4s) are four-stranded structures in guanine-rich genomic regions.
• G4s play crucial roles in regulating gene expression and DNA replication.
• Understanding G4 folding, dynamics, and localization is vital for biological insights.

Purpose of the Study:

• To develop novel fluorescent probes for detecting G-quadruplex DNA structures.
• To investigate the properties and cellular applications of β-carboline-based G4 probes.

Main Methods:

• Synthesis and characterization of β-carboline derivatives as fluorescent probes.
• Spectroscopic analysis (fluorescence enhancement, quantum yield, binding constants) of probe-G4 interactions.
• Cellular imaging in HeLa cells to determine subcellular localization (nucleoli, cytoplasm).

Main Results:

• The lead probe, BCC, demonstrated significant fluorescence enhancement (up to 18-fold) upon binding G4 DNA.
• BCC exhibited a high quantum yield (40%) and strong binding affinity (10^6 M⁻¹) for G4 structures.
• Cellular imaging revealed BCC localizes to nucleoli (rDNA) and cytoplasm (mitochondrial DNA), indicating G4 interactions in these compartments.

Conclusions:

• β-carboline derivatives serve as effective fluorescent probes for G-quadruplex DNA.
• The BCC probe enables sensitive detection and visualization of G4 structures in cellular environments.
• These probes hold potential for applications in studying G4-mediated biological processes.