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Human Telomere Sequence DNA in Water-Free and High-Viscosity Solvents: G-Quadruplex Folding Governed by Kramers Rate Theory

Structures formed by human telomere sequence (HTS) DNA are of interest due to the implication of telomeres in the aging process and cancer. We present studies of HTS DNA folding in an anhydrous, high viscosity deep eutectic solvent (DES) comprised of choline choride and urea. In this solvent, the HTS DNA forms a G-quadruplex with the parallel-stranded (“propeller”) fold, consistent with observations that reduced water activity favors the parallel fold, whereas alternative folds are favored at high water activity. Surprisingly, adoption of the parallel structure by HTS DNA in the DES, after thermal denaturation and quick cooling to room temperature, requires several months, as opposed to less than 2 min in an aqueous solution. This extended folding time in the DES is, in part, due to HTS DNA becoming kinetically trapped in a folded state that is apparently not accessed in lower viscosity solvents. A comparison of times required for the G-quadruplex to convert from its aqueous-preferred folded state to its ...

Authors:   Ford M. Lannan; Irena Mamajanov; Nicholas V. Hud
Journal:   Journal of the American Chemical Society
Year:   2012
DOI:   10.1021/ja303499m
Publication date:   01-06-2012

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