Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Nucleic Acids in Anhydrous Media: G-quadruplex Folding Governed by Kramers Rate Theory
Structures formed by human telomere sequence (HTS) DNA are of interest due to the G-quadruplex forming human telomere sequence (HTS) DNA 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 choride and urea. Under these conditions HTS adopts an extremely stable “parallel-propeller” from of G-quadruplex, consistent with 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 miliseconds 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 τ ~ 1/ƞ1.4 This diffusion control over HTS folding is consistent with Kramers rate theory and these findings highlight the neccesity 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.
This work was jointly supported by NSF and the NASA Astrobiology Program, under the NSF Center for Chemical Evolution, CHE-1004570.
School of Chemistry and Biochemistry