Synthesis of Novel Flavone-Based Ligands with Pyridine Side Chains for DNA Triplex Stabilization
Poster Number
24B
Faculty Mentor Name
Liang Xue
Format
Poster Presentation
Research or Creativity Area
Natural Sciences
Abstract
Triplex DNA is a unique three-stranded nucleic acid structure that forms when a triplex- forming oligonucleotide (TFO) binds to the major groove of duplex DNA through Hoogsteen hydrogen bonding. Interest in triplex DNA has grown due to its potential applications in antigene therapy, where it can selectively bind to genomic regions to inhibit transcription and regulate gene expression, offering a promising approach for treating genetic diseases and cancer. However, the therapeutic application of triplex DNA has been limited by its inherent instability, largely due to electrostatic repulsion between the negatively charged phosphodiester backbones.
Previous work in our group has shown that 5-substituted quercetin derivatives effectively stabilize triplex DNA with minimal effects on duplex stability. Building on this finding, I sought to synthesize a new series of derivatives by attaching a pyridine moiety to the quercetin scaffold through carbon linkers of varying lengths. The planar flavone core allows for intercalation between DNA base triplets, while the pyridine group is designed to extend into the minor groove and provide additional stabilizing interactions. By varying the linker length, we aim to optimize the positioning and flexibility of the pyridine group to enhance triplex DNA stability.
The synthesized ligands were fully characterized using NMR, IR, and MALDI-TOF mass spectrometry. The synthesis scheme and purification methods will be discussed in this presentation.
Location
University of the Pacific, DeRosa University Center
Start Date
24-4-2026 11:00 AM
End Date
24-4-2026 2:00 PM
Synthesis of Novel Flavone-Based Ligands with Pyridine Side Chains for DNA Triplex Stabilization
University of the Pacific, DeRosa University Center
Triplex DNA is a unique three-stranded nucleic acid structure that forms when a triplex- forming oligonucleotide (TFO) binds to the major groove of duplex DNA through Hoogsteen hydrogen bonding. Interest in triplex DNA has grown due to its potential applications in antigene therapy, where it can selectively bind to genomic regions to inhibit transcription and regulate gene expression, offering a promising approach for treating genetic diseases and cancer. However, the therapeutic application of triplex DNA has been limited by its inherent instability, largely due to electrostatic repulsion between the negatively charged phosphodiester backbones.
Previous work in our group has shown that 5-substituted quercetin derivatives effectively stabilize triplex DNA with minimal effects on duplex stability. Building on this finding, I sought to synthesize a new series of derivatives by attaching a pyridine moiety to the quercetin scaffold through carbon linkers of varying lengths. The planar flavone core allows for intercalation between DNA base triplets, while the pyridine group is designed to extend into the minor groove and provide additional stabilizing interactions. By varying the linker length, we aim to optimize the positioning and flexibility of the pyridine group to enhance triplex DNA stability.
The synthesized ligands were fully characterized using NMR, IR, and MALDI-TOF mass spectrometry. The synthesis scheme and purification methods will be discussed in this presentation.
