Naphthalene Diimides Carrying Two β-Cyclodextrins Prefer Telomere RNA G-Quadruplex Recognition.

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Biophysical Chemistry

Background:

• G-quadruplexes are four-stranded nucleic acid structures implicated in various cellular processes.
• Specific recognition and stabilization of G-quadruplex structures are crucial for developing targeted therapeutics.
• Naphthalene diimide (NDI) derivatives are known for their ability to interact with nucleic acids.

Purpose of the Study:

• To synthesize and characterize novel naphthalene diimide derivatives functionalized with β-cyclodextrins (NDI-β-CyDs).
• To investigate the binding affinity and specificity of NDI-β-CyDs towards different G-quadruplex structures.
• To elucidate the molecular interactions governing the binding of NDI-β-CyDs to G-quadruplexes.

Main Methods:

• Chemical synthesis of NDI-β-CyDs.
• Spectroscopic techniques (e.g., UV-Vis, fluorescence) for binding studies.
• Molecular docking and simulation for interaction analysis.

Main Results:

• NDI-β-CyDs were successfully synthesized.
• The compounds exhibited enhanced specificity for parallel and hybrid G-quadruplex structures.
• Highest binding affinity was observed for the telomere RNA G-quadruplex.
• Binding simulations suggested inclusion of loop nucleobases within the β-cyclodextrin cavity.

Conclusions:

• NDI-β-CyDs represent a promising class of ligands for selective G-quadruplex recognition.
• The β-cyclodextrin moieties contribute to the specificity and affinity of the NDI core.
• These findings open avenues for developing novel G-quadruplex-targeting agents.