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Convenient and Efficient Syntheses of Oligodeoxyribonucleotides Containing O 6-(Carboxymethyl)Guanine and O 6-(4-Oxo-4-(3-Pyridyl)Butyl)Guanine |
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| Authors: | Christopher L. Millington Amanda J. Watson Andrew S. Marriott Geoffrey P. Margison Andrew C. Povey David M. Williams |
| Affiliation: | 1. Centre for Chemical Biology, Department of Chemistry , Krebs Institute, University of Sheffield , Sheffield , S3 7HF , UK;2. Cancer Research—UK Carcinogenesis Group , Paterson Institute for Cancer Research , Manchester , M20 4BX , UK;3. Centre for Occupational &4. Environmental Health, Faculty of Medical &5. Human Sciences , University of Manchester , Manchester , M13 9PL , UK |
| 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. [Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids to view the free supplemental file.] |
| Keywords: | O 6-(Carboxymethyl)guanine O 6-(4-oxo-4-(3-pyridyl)butyl)guanine DNA synthesis alkyltransferase-like protein |