Development of Potent DNA Triplex Binding Ligands by Expanding Aromatic Surface
Poster Number
3C
Introduction/Abstract
Triple helical DNA is a DNA structure in which three oligonucleotides wind around each other by forming Hoogsteen base pairs either intra- or intermolecularly. Intramolecular triplex DNA (H-DNA) is formed in supercoiled DNAs with homopurine and homopyrimidine strands with mirror repeat symmetry. Intermolecular triplex occurs between a duplex and a neighboring chromosome or a triplex-forming oligonucleotide (TFO). The use of a TFO is promising in anti-gene therapy because it will bind to a targeted duplex DNA site in a sequence-specific manner. However, the association of a TFO with a duplex is thermodynamically less favorable and kinetically slower than its counterpart duplex formation. Anti-gene enhancers are small molecules that can facilitate triplex formation via intercalation or groove binding. Our research group has recently discovered two novel quercetin derivatives that show strong binding toward the triplex while having minimal effect on the duplex DNA.
Purpose
Based on the previous findings, I design and synthesize novel quercetin derivatives by expanding aromatic surface areas. An increase in the surface area of a ligand should give better π–π stacking interactions between the ligand and the nucleobases in triplex DNA, resulting in a more potent and specific triplex binding ligand. In this poster presentation, the synthesis procedures and characterizations of target molecules will be discussed.
Method
The target compounds and their precursors were synthesized using standard organic synthesis methods. They were purified using flash column chromatography and characterized using 1H and 13C NMR.
Results
The 1H and 13C NMR spectra show the correct structures of the two precursors.
Significance
I design and synthesize novel quercetin derivatives by expanding aromatic surface areas. An increase in the surface area of a ligand should give better π–π stacking interactions between the ligand and the nucleobases in triplex DNA, resulting in a more potent and specific triplex binding ligand. My research can have a significant impact on anti-gene therapy.
Location
William Knox Holt Memorial Library and Learning Center, University of the Pacific, 3601 Pacific Ave., Stockton, CA 95211
Format
Poster Presentation
Poster Session
Afternoon
Development of Potent DNA Triplex Binding Ligands by Expanding Aromatic Surface
William Knox Holt Memorial Library and Learning Center, University of the Pacific, 3601 Pacific Ave., Stockton, CA 95211
Triple helical DNA is a DNA structure in which three oligonucleotides wind around each other by forming Hoogsteen base pairs either intra- or intermolecularly. Intramolecular triplex DNA (H-DNA) is formed in supercoiled DNAs with homopurine and homopyrimidine strands with mirror repeat symmetry. Intermolecular triplex occurs between a duplex and a neighboring chromosome or a triplex-forming oligonucleotide (TFO). The use of a TFO is promising in anti-gene therapy because it will bind to a targeted duplex DNA site in a sequence-specific manner. However, the association of a TFO with a duplex is thermodynamically less favorable and kinetically slower than its counterpart duplex formation. Anti-gene enhancers are small molecules that can facilitate triplex formation via intercalation or groove binding. Our research group has recently discovered two novel quercetin derivatives that show strong binding toward the triplex while having minimal effect on the duplex DNA.
