Synthesis of Oligodeoxynucleotides Containing a C8-2'-Deoxyguanosine Adduct Formed by the Carcinogen 3-Nitrobenzanthrone

Curr Protoc Nucleic Acid Chem. 2017 Jun 19:69:4.73.1-4.73.15. doi: 10.1002/cpnc.28.

Abstract

This unit describes the detailed procedure in five parts for the synthesis of the C8-2'-deoxyguanosine-3-aminobenzanthrone adduct located in a desired site in an oligonucleotide. The synthesis of the protected 2'-deoxyguanosine, O6 -benzyl-N2 -DMTr-3'-5'-bisTBDMS-C8-Br-2'-deoxyguanosine, is described in the first part. The synthesis of the reduced carcinogen 3-aminobenzanthrone is detailed in part two. The third part outlines the key step of the adduct formation between the reduced carcinogen and the protected nucleoside by a palladium-catalyzed cross coupling reaction. The final two parts describe phosphoramidite synthesis from the nucleoside-carcinogen adduct followed by its site-specific incorporation into DNA by solid-phase oligonucleotide synthesis. The adducted oligonucleotides are purified by reversed-phase HPLC and characterized by mass spectrometry. © 2017 by John Wiley & Sons, Inc.

Keywords: C8 guanine adduct; DNA adduct; DNA lesion bypass; cross coupling; environmental carcinogen; palladium-catalyzed.

MeSH terms

  • Automation
  • Benz(a)Anthracenes / chemistry*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Carcinogens / chemistry*
  • Deoxyguanosine / chemistry*
  • Oligodeoxyribonucleotides / chemical synthesis*
  • Oligodeoxyribonucleotides / chemistry
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Benz(a)Anthracenes
  • Carcinogens
  • Oligodeoxyribonucleotides
  • Deoxyguanosine
  • 3-nitrobenzanthrone