Design, Synthesis, and Analysis of Substituted Flavones: Exploring Substitution Position Modifications Inspired by Quercetin Derivatives
Poster Number
21C
Faculty Mentor Name
Dr. Liang Xue
Format
Poster Presentation
Research or Creativity Area
Other
Abstract
DNA triplexes are three-stranded DNA structures that can form both intramolecularly and intermolecularly. Intramolecular triplexes occur when a single DNA strand folds onto a duplex DNA with Hoogsteen hydrogen bonding, while intermolecular triplexes form when an external triplex-forming oligonucleotide (TFO) binds to a duplex DNA target through Hoogsteen interactions. Because the formation of triplex is highly sequence specific, TFO-mediated DNA recognition has attracted significant interest as a potential anti-gene strategy for controlling gene expression at the DNA level. However, triplex formation is unfavorable under physiological conditions due to electrostatic repulsion among the three negatively charged strands. Previous studies from our group identified naturally occurring flavonoids, found in many fruits and vegetables, as promising small molecule ligands for triplex stabilization. Notably, 5-substituted quercetin derivatives were found to selectively stabilize DNA triplexes while leaving duplex DNA unaffected. Building on these findings, I synthesized a series of eighteen flavone derivatives with different functional groups at varying positions on the flavone scaffold. These compounds were designed to probe structure-activity relationships to the 5-substituted quercetin analogs. All derivatives were fully characterized by NMR and mass spectrometry. Their ability to stabilize triplex DNA was evaluated using UV-monitored thermal denaturation. Binding affinities and thermodynamic parameters were quantified using isothermal titration calorimetry (ITC).
Purpose
The purpose of this work is to synthesize and evaluate flavone derivatives with varying functional groups to investigate how structural modifications influence DNA triplex stabilization.
Location
University of the Pacific, DeRosa University Center
Start Date
24-4-2026 11:00 AM
End Date
24-4-2026 2:00 PM
Design, Synthesis, and Analysis of Substituted Flavones: Exploring Substitution Position Modifications Inspired by Quercetin Derivatives
University of the Pacific, DeRosa University Center
DNA triplexes are three-stranded DNA structures that can form both intramolecularly and intermolecularly. Intramolecular triplexes occur when a single DNA strand folds onto a duplex DNA with Hoogsteen hydrogen bonding, while intermolecular triplexes form when an external triplex-forming oligonucleotide (TFO) binds to a duplex DNA target through Hoogsteen interactions. Because the formation of triplex is highly sequence specific, TFO-mediated DNA recognition has attracted significant interest as a potential anti-gene strategy for controlling gene expression at the DNA level. However, triplex formation is unfavorable under physiological conditions due to electrostatic repulsion among the three negatively charged strands. Previous studies from our group identified naturally occurring flavonoids, found in many fruits and vegetables, as promising small molecule ligands for triplex stabilization. Notably, 5-substituted quercetin derivatives were found to selectively stabilize DNA triplexes while leaving duplex DNA unaffected. Building on these findings, I synthesized a series of eighteen flavone derivatives with different functional groups at varying positions on the flavone scaffold. These compounds were designed to probe structure-activity relationships to the 5-substituted quercetin analogs. All derivatives were fully characterized by NMR and mass spectrometry. Their ability to stabilize triplex DNA was evaluated using UV-monitored thermal denaturation. Binding affinities and thermodynamic parameters were quantified using isothermal titration calorimetry (ITC).
Comments
Dr. Liang Xue is the advisor