The conformational effect of para-substituted C8-arylguanine adducts on the B/Z-DNA equilibrium

The B form of DNA exists in equilibrium with the Z form and is mainly affected by sequence, electrostatic interactions, and steric effects. C8-purine substitution shifts the equilibrium toward the Z form though how this interaction overcomes the unfavorable electrostatic interactions and decrease in stacking in the Z form has not been determined. Here, a series of C8-arylguanine derivatives, bearing a para-substituent were prepared and the B/Z equilibrium determined. B/Z ratios were measured by CD and conformational effects of the aryl substitution determined by NMR spectroscopy and molecular modeling. The para-substituent was found to have a significant effect on the B/Z DNA equilibrium caused by altering base-pair stacking of the B form and modifying the hydration/ion shell of the B form. A unique melting temperature versus salt concentration was observed and provides evidence relevant to the mechanism of B/Z conformational interconversion.

Graphical AbstractResearch Highlights►C8-guanine arylation causes B/Z DNA equilibrium to shift to Z form. ►Position of equilibrium strongly depends on the aryl para-substituent. ►Arylation disrupts hydration shell and destabilizes the B form. ►Novel salt concentration dependence of melting temperature.