NRAS DNA G-quadruplex-targeting molecules for sequence-selective enzyme inhibition

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• G-quadruplex structures are important in gene regulation.
• Developing selective ligands for specific G-quadruplexes is challenging but valuable for controlling gene expression.

Purpose of the Study:

• To establish a novel fluorescence displacement assay for identifying sequence-selective G-quadruplex ligands.
• To identify ligands that specifically target the NRAS G-quadruplex DNA structure.

Main Methods:

• Development of a NRAS G-quadruplex selective fluorescent probe.
• Utilizing a fluorescence displacement assay to screen for potential ligands.
• Testing ligand binding affinity in the presence of competing DNA structures (e.g., human telomeric G-quadruplex).

Main Results:

• Successfully established a new fluorescence displacement assay.
• Identified sequence-selective G-quadruplex ligands targeting NRAS.
• Demonstrated that these ligands maintain binding affinity against high concentrations of human telomeric G-quadruplex DNA.
• Showcased sequence-selective regulation of enzymatic activities by the identified ligands.

Conclusions:

• The developed assay is effective for discovering sequence-selective G-quadruplex ligands.
• The identified NRAS G-quadruplex ligands hold potential for precise gene expression control.
• These ligands exhibit specificity, offering a promising tool for therapeutic applications targeting specific DNA structures.