1,N2-Etheno-2'-deoxyguanosine adopts the syn conformation about the glycosyl bond when mismatched with deoxyadenosine

Chem Res Toxicol. 2011 Jul 18;24(7):1071-9. doi: 10.1021/tx200089v. Epub 2011 Jun 16.


The oligodeoxynucleotide 5'-CGCATXGAATCC-3'·5'-GGATTCAATGCG-3' containing 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-εdG) opposite deoxyadenosine (named the 1,N(2)-εdG·dA duplex) models the mismatched adenine product associated with error-prone bypass of 1,N(2)-εdG by the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) and by Escherichia coli polymerases pol I exo(-) and pol II exo(-). At pH 5.2, the T(m) of this duplex was increased by 3 °C as compared to the duplex in which the 1,N(2)-εdG lesion is opposite dC, and it was increased by 2 °C compared to the duplex in which guanine is opposite dA (the dG·dA duplex). A strong NOE between the 1,N(2)-εdG imidazole proton and the anomeric proton of the attached deoxyribose, accompanied by strong NOEs to the minor groove A(20) H2 proton and the mismatched A(19) H2 proton from the complementary strand, establish that 1,N(2)-εdG rotated about the glycosyl bond from the anti to the syn conformation. The etheno moiety was placed into the major groove. This resulted in NOEs between the etheno protons and T(5) CH(3). A strong NOE between A(20) H2 and A(19) H2 protons established that A(19), opposite to 1,N(2)-εdG, adopted the anti conformation and was directed toward the helix. The downfield shifts of the A(19) amino protons suggested protonation of dA. Thus, the protonated 1,N(2)-εdG·dA base pair was stabilized by hydrogen bonds between 1,N(2)-εdG N1 and A(19) N1H(+) and between 1,N(2)-εdG O(9) and A(19)N(6)H. The broad imino proton resonances for the 5'- and 3'-flanking bases suggested that both neighboring base pairs were perturbed. The increased stability of the 1,N(2)-εdG·dA base pair, compared to that of the 1,N(2)-εdG·dC base pair, correlated with the mismatch adenine product observed during the bypass of 1,N(2)-εdG by the Dpo4 polymerase, suggesting that stabilization of this mismatch may be significant with regard to the biological processing of 1,N(2)-εdG.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Pair Mismatch
  • DNA Polymerase I / metabolism
  • DNA Polymerase II / metabolism
  • DNA Polymerase beta / metabolism
  • Deoxyadenosines / chemistry*
  • Escherichia coli / enzymology
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Oligodeoxyribonucleotides / chemistry
  • Protons
  • Sulfolobus solfataricus / enzymology
  • Transition Temperature


  • Deoxyadenosines
  • Oligodeoxyribonucleotides
  • Protons
  • 1,N(6)-ethenodeoxyadenosine
  • DNA Polymerase I
  • DNA Polymerase II
  • DNA Polymerase beta