Stabilization of Triplex DNA by Flavone Derivatives with Pyridine-containing Side Chains
Faculty Mentor Name
Liang Xue
Research or Creativity Area
Natural Sciences
Abstract
Triplex DNA structures form when a third oligonucleotide strand binds to duplex DNA through Hoogsteen hydrogen bonding within the major groove. These structures are both naturally and/or artificially occurring in vivo and involved in several biological processes, including, but not limited to, gene regulation, DNA replication, and DNA repair. Forming a triple-helical structure by targeting duplex DNA with a triplex-forming oligonucleotide (TFO) in a sequence-specific manner illustrates a promising strategy for the regulation of gene transcription, more commonly known as the antigene strategy. However, triplex DNAs’ slow formation and low stability limit its use as antigene agents. A possible pathway to increase stability, in addition to facilitating triplex formation, is through a use of small molecules. The Xue group has recently reported a series of triplex-specific binding ligands which were derived from plant-based compounds known as flavones. Various studies in the biophysical realm suggest that these ligands have a high selectivity/affinity for triplex DNA compared to duplex DNA, specifically when an amino-containing side chain is present at the 5-position of the ‘flavone scaffold’. We hope to advance these studies by introducing pyridine containing side chains at the 5-position to demonstrate its ability to enhance triplex stability. In this poster, we present synthesis, characterization, and biophysical evaluation of these molecules, demonstrating their ability to enhance triplex stability.
Stabilization of Triplex DNA by Flavone Derivatives with Pyridine-containing Side Chains
Triplex DNA structures form when a third oligonucleotide strand binds to duplex DNA through Hoogsteen hydrogen bonding within the major groove. These structures are both naturally and/or artificially occurring in vivo and involved in several biological processes, including, but not limited to, gene regulation, DNA replication, and DNA repair. Forming a triple-helical structure by targeting duplex DNA with a triplex-forming oligonucleotide (TFO) in a sequence-specific manner illustrates a promising strategy for the regulation of gene transcription, more commonly known as the antigene strategy. However, triplex DNAs’ slow formation and low stability limit its use as antigene agents. A possible pathway to increase stability, in addition to facilitating triplex formation, is through a use of small molecules. The Xue group has recently reported a series of triplex-specific binding ligands which were derived from plant-based compounds known as flavones. Various studies in the biophysical realm suggest that these ligands have a high selectivity/affinity for triplex DNA compared to duplex DNA, specifically when an amino-containing side chain is present at the 5-position of the ‘flavone scaffold’. We hope to advance these studies by introducing pyridine containing side chains at the 5-position to demonstrate its ability to enhance triplex stability. In this poster, we present synthesis, characterization, and biophysical evaluation of these molecules, demonstrating their ability to enhance triplex stability.
