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.
Department of Pharmaceutical and Pharmacological Sciences, West Virginia University, PO Box 9530, Morgantown, WV 26506, United States. Vorasit.v@chula.ac.th
Vorasit
V
Vongsutilers
Daniel J
DJ
Phillips
Brian C
BC
Train
Gregory R
GR
McKelvey
Nissa M
NM
Thomsen
Kevin H
KH
Shaughnessy
James P
JP
Lewis
Peter M
PM
Gannett
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D043542:DNA, Z-Form / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry; D013816:Thermodynamics
D043542:DNA, Z-Form; D009841:Oligonucleotides; D006147:Guanine; D004247:DNA