49 Nucleic acids in anhydrous media: G-quadruplex folding governed by Kramers rate theory

Abstract

Structures formed by human telomere sequence (HTS) DNA are of interest due to G-quadruplex forming HTS DNA that has recently generated a tremendous interest due to its involvement in aging process and cancer. The present study examines HTS in anhydrous, exceptionally viscous deep eutectic solvent (DES), comprised of choline, chloride, and urea. Under these conditions, HTS adopts an extremely stable “parallel-propeller” form of G-quadruplex, consistent with the previously observed effects of diminished water activity. Additionally, the high solvent friction of DES slows the dynamics of HTS folding on the order of months, as opposed to milliseconds in aqueous solution, and allows the entrapment of kinetic intermediates. Moreover, analogous transition studies of the quadruplex converting from the aqueous buffer structure to the parallel form in 90% DES (w/v) and 40% PEG 200 (v/v) differ from hours to days scaling inversely with viscosity ∼ 1/ƞ1.4. This diffusion control over the HTS folding is consistent with Kramers rate theory and these findings highlight the necessity to consider the viscosity of intracellular conditions when exploring the structure dynamics of telomeres and drug binding interactions. Lastly, tuning solvent viscosity could prove useful in the future study of G-quadruplex dynamics, and applied DNA nano-technology, where time dependent structural transitions are desired.