Insights into the DNA stabilizing contributions of a bicyclic cytosine analogue: crystal structures of DNA duplexes containing 7,8-dihydropyrido [2,3-d]pyrimidin-2-one

Nucleic Acids Res. 2010 Oct;38(19):6737-45. doi: 10.1093/nar/gkq519. Epub 2010 Jun 16.

Abstract

The incorporation of the bicyclic cytosine analogue 7,8-dihydropyrido[2,3-d]pyrimidin-2-one (X) into DNA duplexes results in a significant enhancement of their stability (3-4 K per modification). To establish the effects of X on the local hydrogen-bonding and base stacking interactions and the overall DNA conformation, and to obtain insights into the correlation between the structure and stability of X-containing DNA duplexes, the crystal structures of [d(CGCGAATT-X-GCG)](2) and [d(CGCGAAT-X-CGCG)](2) have been determined at 1.9-2.9 Å resolutions. In all of the structures, the analogue X base pairs with the purine bases on the opposite strands through Watson-Crick and/or wobble type hydrogen bonds. The additional ring of the X base is stacked on the thymine bases at the 5'-side and overall exhibits greatly enhanced stacking interactions suggesting that this is a major contribution to duplex stabilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • Crystallography, X-Ray
  • Cytosine / analogs & derivatives*
  • Cytosine / chemistry
  • DNA / chemistry*
  • Fluorescent Dyes / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular*
  • Nucleic Acid Conformation

Substances

  • 7,8-dihydropyrido(2,3-d)pyrimidin-2-one
  • Fluorescent Dyes
  • Cytosine
  • DNA

Associated data

  • PDB/3GJH
  • PDB/3N4N
  • PDB/3N4O