| 'G' rich DNA/RNA sequences can form four stranded structures called quadruplexes which are further stabilized by K+/Na + ions. Significant amount of research efforts on these structures are being focused on their ability to interfere with telomere maintenance by inhibiting telomerase which is one of the hallmarks of cancer. There are many convincing research evidences that show the presence of a quadruplex/quadruplex-small molecule complex can inhibit telomerase. Recently, there have been numerous research findings that suggest that the formation of quadruplex structures occurs in the promoter regions and modulates gene expression. This expands the potential therapeutic significance of quadruplex structures. These research findings have kindled the exploration of small molecules that interact with quadruplex structures.;Structural studies of various quadruplex structures and their complexes with small molecules have been investigated using a variety of biophysical techniques such as circular dichroism, NMR spectroscopy, fluorescence spectroscopy and footprinting. CD and fluorescence studies of various quadruplex structures with NMM, DODC and DTDC revealed that these molecules show different levels of selectivity towards different quadruplex structures. A mix and measure fluorescence screening method was developed here for the exploration of selective quadruplex binders. NMR spectroscopic investigations of human telomeric quadruplex DNA, 24mer-DTDC complex were performed. For the first time, the application of hydroxyl radical footprinting was used to study quadruplex structures and their complexes with small molecules. |
