Convenient and efficient syntheses of oligodeoxyribonucleotides containing O(6)-(carboxymethyl)guanine and O(6)-(4-oxo-4-(3-pyridyl)butyl)guanine

Nucleosides Nucleotides Nucleic Acids. 2012 Apr;31(4):328-38. doi: 10.1080/15257770.2012.656784.

Abstract

O(6)-(carboxymethyl)guanine (O(6)-CMG) and O(6)-(4-oxo-4-(3-pyridyl)butyl)guanine (O(6)-pobG) are toxic lesions formed in DNA following exposure to alkylating agents. O(6)-CMG results from exposure to nitrosated glycine or nitrosated bile acid conjugates and may be associated with diets rich in red meat. O(6)-pobG lesions are derived from alkylating agents found in tobacco smoke. Efficient syntheses of oligodeoxyribonucleotides (ODNs) containing O(6)-CMG and O(6)-pobG are described that involve nucleophilic displacement by the appropriate alcohol on a common synthetic ODN containing the reactive base 2-amino-6-methylsulfonylpurine. ODNs containing O(6)-pobG and O (6)-CMG were found to be good substrates for the S. pombe alkyltransferase-like protein Atl1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / metabolism
  • Base Sequence
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Oligodeoxyribonucleotides / chemical synthesis*
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism

Substances

  • O(6)-(4-oxo-4-(3-pyridyl)butyl)guanine
  • Oligodeoxyribonucleotides
  • Guanine
  • ATL1 protein, S pombe
  • Alkyl and Aryl Transferases