Guanine-rich telomeric DNA at the end of chromosomes can form a unique DNA secondary structure - G-quadruplex, which is known to inhibit the binding of telomerase to telomeric regions in cancer cells and thus regulate unrestricted cancer cell growth. Hence, G-quadruplex DNA has recently become a promising target in oncology. The formation of G-quadruplex structures is greatly facilitated by G-quadruplex binding ligands such as Thiazole orange (TO). Upon binding to DNA, the fluorescence of TO can increase up to 1000-fold, making it an attractive probe for studying ligand-DNA interactions. However, the selectivity of TO binding to duplex and G-quadruplex DNA is minimal. In the present work, we investigated the feasibility of increasing the TO binding selectivity toward G-quadruplex DNA by introducing side chains that could enhance the binding specificity. TO derivatives containing various side chains were synthesized and their binding to G-quadruplex DNA was evaluated using fluorescence thermal denaturation and circular dichroism. The synthesis of TO derivatives and biophysical measurements will be presented.

Synthesis and biophysical evaluation of thiazole orange derivatives as DNA G-quadruplex binding ligands

243rd National Meeting (2012)

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