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

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.