Selectively recognizing heptad-interfaced G-quadruplexes by a molecular rotor with an ESIPT emission

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Biophysical Chemistry

Background:

• G-quadruplexes (G4s) are non-canonical DNA structures implicated in gene regulation.
• The c-myb proto-oncogene promoter contains GGA repeats capable of forming G4 structures.
• Targeting G4s offers a strategy for modulating gene expression.

Purpose of the Study:

• To investigate the selective targeting of heptad-interfaced G-quadruplexes by sophoflavescenol (Sop).
• To elucidate the photophysical mechanism underlying the interaction between Sop and G4s.
• To explore the potential of Sop-induced emission for G4 detection.

Main Methods:

• Synthesis and characterization of prenylated flavonol sophoflavescenol (Sop).
• G-quadruplex formation assays using GGA repeats from the c-myb promoter.
• Spectroscopic studies (UV-Vis, fluorescence) to analyze molecular interactions.
• Investigation of excited state intramolecular proton transfer (ESIPT) phenomena.

Main Results:

• Sophoflavescenol (Sop) selectively binds to heptad-interfaced G-quadruplexes (G4s) in the c-myb promoter.
• Binding of Sop restricts molecular rotation, leading to enhanced fluorescence.
• A strong excited state intramolecular proton transfer (ESIPT) emission is triggered upon Sop binding.
• The observed ESIPT emission is dependent on the G4 structure and Sop's molecular conformation.

Conclusions:

• Sophoflavescenol is a potent and selective ligand for c-myb G-quadruplexes.
• The restricted molecular rotation and ESIPT emission provide a sensitive readout for G4 recognition.
• This study presents a novel molecular mechanism for G4 targeting with potential applications in diagnostics and therapeutics.