Understanding the conformations and stabilities of g-quadruplexes formed by human telomere sequence in ideal and less ideal solutions




Sharma, Vishal Rajat

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The G-rich termini of human chromosomes, called telomeres, have the ability to form unique DNA structures called G-Quadruplexes, which have been implicated in certain cancer types and, as a result, have drawn researchers' attention to study their structure inside the cell and thus consider them as potential targets for new anticancer therapies. Biophysical studies of these entities have been carried out under near ideal conditions, i.e., low phosphate concentration (e.g., 10mM), pH 7, low ionic strength (e.g., 115mM), and for optical studies, low concentration of DNA (e.g., 1 × 10-6 M). We, here, created less ideal conditions by using different osmolytes such as polyethylene glycol, acetonitrile, trifluoroethanol, and betaine. Our research focuses on the effect of these co-solutes on the structural and thermodynamic properties of telomeric DNA oligomers and report the characterization of (TTAGGG)x, where x = 1, 2, or 4. In general, increasing the percentage of any osmolytes in solutions drives the equilibrium from unimolecular hybrid to multimolecular parallel conformation. In addition, Stability of parallel conformation also increases.



Molecular biology, Biochemistry, Biophysics, Pure sciences, Chemistry