Benzoselenazolium-based hemicyanine dye for G-Quadruplex detection

Area of Science:

• Chemical Biology
• Molecular Probes
• Nucleic Acid Structures

Background:

• Hemicyanine dyes are commonly synthesized using benzothiazolium and benzoxazolium moieties.
• The isosteric analogue, benzoselenazolium, has been underexplored in dye development.
• Selective detection of G-quadruplexes is crucial for understanding their biological roles.

Purpose of the Study:

• To develop the first benzoselenazolium-based hemicyanine dye.
• To create a fluorescent probe for the selective detection of G-quadruplexes.
• To investigate the probe's utility in cellular imaging.

Main Methods:

• Synthesis and characterization of a novel benzoselenazolium-based hemicyanine dye (SEMA-1).
• Validation of SEMA-1 as an activatable, red-emitting fluorescent probe in buffer solutions.
• Cellular imaging studies using fixed and live HeLa cells to assess probe localization and detection capabilities.

Main Results:

• SEMA-1 exhibits fluorescence activation specifically in the presence of G-quadruplexes.
• The probe accumulates in the nucleoli of fixed HeLa cells, detecting G-quadruplexes in rDNA and rRNA.
• In live HeLa cells, SEMA-1 is captured by mitochondria, indicating potential for detecting mitochondrial G-quadruplexes.

Conclusions:

• Benzoselenazolium-based hemicyanine scaffolds are valuable for developing novel G-quadruplex-specific fluorescent probes.
• SEMA-1 represents a promising tool for visualizing G-quadruplexes in various cellular compartments.
• This study highlights the potential of exploring isosteric analogues for advanced molecular probe design.