Synthesis of Thiazole Orange derivatives as DNA G-quadruplex binding ligands
Poster Number
23
Format
Poster Presentation
Faculty Mentor Name
Liang Xue
Faculty Mentor Department
Chemistry
Abstract/Artist Statement
G-quadruplex, a unique DNA secondary structure that inhibits the telomerase activity at the end of the chromosomes, has become a novel target in oncology in recent years. The formation of G-quadruplex structures is facilitated by small molecules (G-quadruplex binding ligands) that contain extended and fused aromatic rings. Thiazole Orange (TO), an example of G-quadruplex binding ligands, is known to bind to both DNA duplex and G-quadruplex. Upon binding, TO fluoresces, which makes it an attractive probe for studying ligand-DNA interactions. However, the selectivity of TO binding to DNA duplex and G-quadruplex is minimal. In the present work, we sought to investigate the feasibility to increase the TO selectivity toward G-quadruplex DNA by introducing side chains to enhance the binding specificity. TO derivatives containing various side chains were synthesized and their binding to G-quadruplex DNA was evaluated using UV denaturation. The synthesis of TO derivatives and biophysical measurements will be presented.
Location
DeRosa University Center, Ballroom
Start Date
21-4-2011 6:00 PM
End Date
21-4-2011 8:00 PM
Synthesis of Thiazole Orange derivatives as DNA G-quadruplex binding ligands
DeRosa University Center, Ballroom
G-quadruplex, a unique DNA secondary structure that inhibits the telomerase activity at the end of the chromosomes, has become a novel target in oncology in recent years. The formation of G-quadruplex structures is facilitated by small molecules (G-quadruplex binding ligands) that contain extended and fused aromatic rings. Thiazole Orange (TO), an example of G-quadruplex binding ligands, is known to bind to both DNA duplex and G-quadruplex. Upon binding, TO fluoresces, which makes it an attractive probe for studying ligand-DNA interactions. However, the selectivity of TO binding to DNA duplex and G-quadruplex is minimal. In the present work, we sought to investigate the feasibility to increase the TO selectivity toward G-quadruplex DNA by introducing side chains to enhance the binding specificity. TO derivatives containing various side chains were synthesized and their binding to G-quadruplex DNA was evaluated using UV denaturation. The synthesis of TO derivatives and biophysical measurements will be presented.