High-Throughput FRET Melting Analysis of Flavone Derivatives Binding to Telomeric G-Quadruplex DNA
Poster Number
17C
Faculty Mentor Name
Dr. Liang Xue, Nghia Tran, Tiffanie Jiang
Research or Creativity Area
Natural Sciences
Abstract
Building on our previous exploration of triplex-specific DNA ligands, our research group has synthesized an extensive library of flavone-based compounds. The current study shifts our focus toward another biologically significant DNA secondary structures, the G-quadruplex (G4).
G4s are non-canonical structures formed in guanine-rich DNA sequences, particularly within human telomeres and oncogene promoter regions. Stabilizing G4s by small molecules, in principle, could regulate biological functions, such as telomere shortening and downregulation of oncogene expression. Given the extended planar aromatic surfaces of our flavone-based derivatives, we hypothesized they may effectively bind to G-quartets through π-π stacking.
To efficiently evaluate our library’s interaction with telomeric G4 DNA, we transitioned to exploit a new high-throughput fluorescence resonance energy transfer (FRET) melting assay performed in a 96-well plate. This approach allowed for a much larger samples size compared to traditional UV methods.
Purpose
Our objective was to evaluate the G-quadruplex stabilization potential of our flavone-based derivatives, with a specific focus on binding selectivity.
Results
Our studies showed that at a low ligand concentration of 2 µM, most compounds exhibited little to no stabilizing effect. At a high ligand concentration of 10 µM, eleven ligands demonstrated moderate stabilization of the telomeric G4. Interestingly, none of natural flavonoids showed any measurable stabilization.
Significance
G4s represent promising targets for oncology. Stabilization of these structures has been linked to the inhibition of telomere maintenance and the downregulation of oncogene expression.
Location
University of the Pacific, DeRosa University Center
Start Date
24-4-2026 11:00 AM
End Date
24-4-2026 2:00 PM
High-Throughput FRET Melting Analysis of Flavone Derivatives Binding to Telomeric G-Quadruplex DNA
University of the Pacific, DeRosa University Center
Building on our previous exploration of triplex-specific DNA ligands, our research group has synthesized an extensive library of flavone-based compounds. The current study shifts our focus toward another biologically significant DNA secondary structures, the G-quadruplex (G4).
G4s are non-canonical structures formed in guanine-rich DNA sequences, particularly within human telomeres and oncogene promoter regions. Stabilizing G4s by small molecules, in principle, could regulate biological functions, such as telomere shortening and downregulation of oncogene expression. Given the extended planar aromatic surfaces of our flavone-based derivatives, we hypothesized they may effectively bind to G-quartets through π-π stacking.
To efficiently evaluate our library’s interaction with telomeric G4 DNA, we transitioned to exploit a new high-throughput fluorescence resonance energy transfer (FRET) melting assay performed in a 96-well plate. This approach allowed for a much larger samples size compared to traditional UV methods.
