Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT).
Authors
Shibata, TakayukiGlynn, Nicola
McMurry, T Brian H
McElhinney, R Stanley
Margison, Geoffrey P
Williams, David M
Affiliation
Department of Chemistry, Centre for Chemical Biology, Richard Roberts Building, University of Sheffield, Sheffield, S3 7HF, UK.Issue Date
2006
Metadata
Show full item recordAbstract
The human DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O6-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the protein. MGMT also provides resistance of tumours to alkylating agents used in cancer chemotherapy and its inactivation is therefore of particular clinical importance. We describe a post-DNA synthesis strategy which exploits the novel, modified base 2-amino-6-methylsulfonylpurine and allows access for the first time to a wide variety of oligodeoxyribonucleotides (ODNs) containing O6-alkylguanines. One such ODN containing O6-(4-bromothenyl)guanine is the most potent inactivator described to date with an IC50 of 0.1 nM.Citation
Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT). 2006, 34 (6):1884-91 Nucleic Acids Res.Journal
Nucleic Acids ResearchDOI
10.1093/nar/gkl117PubMed ID
16609128Type
ArticleLanguage
enISSN
1362-4962ae974a485f413a2113503eed53cd6c53
10.1093/nar/gkl117