Analysis of Various Functional Groups on Flavone Derivatives for Triplex DNA Binding
Poster Number
6
Faculty Mentor Name
Dr. Liang Xue
Research or Creativity Area
Natural Sciences
Abstract
Triplex DNA is a unique three-stranded DNA structure that can form both intramolecularly and intermolecularly. Intramolecular triplexes occur when a DNA strand folds onto itself, forming Hoogsteen hydrogen bonds, while intermolecular triplexes form when an external third strand, known as a triplex-forming oligonucleotide (TFO), binds to a duplex through Hoogsteen interactions. Interest in triplex DNA has grown due to its potential applications in antigene therapy, where TFOs can selectively bind to genomic regions to regulate gene expression. This offers a promising approach for treating genetic diseases and cancer. Previously, our group found that 5-substituted quercetin derivatives effectively bind to triplex DNA with minimal impact on duplex DNA stability. Building on this work, I focused on synthesizing different flavone derivatives with various functional groups attached to the flavone backbone to investigate their effects on triplex DNA stabilization. Using thermal denaturation monitored by UV spectroscopy, I will present how these modifications influence triplex stability.
Purpose
This project focused on synthesizing different flavone derivatives with various functional groups attached to the flavone backbone. This approach was based on our previous findings that 5-substituted quercetin derivatives selectively stabilize triplex DNA with minimal effect on duplex DNA. By introducing different functional groups, this study aimed to see how these changes affect triplex stability and to identify features that improve selective binding.
Results
A total of 18 flavone derivatives with different functional groups were successfully synthesized, purified, and characterized. Thermal denaturation monitored by UV was used to study their interaction with triplex DNA. The results showed that while some compounds were able to stabilize the triplex structure, they were generally less effective than the previously reported 5-substituted quercetin derivatives.
Significance
This work is important as it investigates how different functional groups on flavone derivatives can enhance triplex DNA stabilization, a key factor in antigene therapy. By improving triplex formation, these compounds may provide a better approach to regulating gene expression, with potential applications in treating genetic diseases and cancer. The findings could contribute to the design of targeted therapies and be shared with researchers in gene therapy and molecular drug development.
Location
University of the Pacific, DeRosa University Center
Start Date
26-4-2025 10:00 AM
End Date
26-4-2025 1:00 PM
Analysis of Various Functional Groups on Flavone Derivatives for Triplex DNA Binding
University of the Pacific, DeRosa University Center
Triplex DNA is a unique three-stranded DNA structure that can form both intramolecularly and intermolecularly. Intramolecular triplexes occur when a DNA strand folds onto itself, forming Hoogsteen hydrogen bonds, while intermolecular triplexes form when an external third strand, known as a triplex-forming oligonucleotide (TFO), binds to a duplex through Hoogsteen interactions. Interest in triplex DNA has grown due to its potential applications in antigene therapy, where TFOs can selectively bind to genomic regions to regulate gene expression. This offers a promising approach for treating genetic diseases and cancer. Previously, our group found that 5-substituted quercetin derivatives effectively bind to triplex DNA with minimal impact on duplex DNA stability. Building on this work, I focused on synthesizing different flavone derivatives with various functional groups attached to the flavone backbone to investigate their effects on triplex DNA stabilization. Using thermal denaturation monitored by UV spectroscopy, I will present how these modifications influence triplex stability.
