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    Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT).

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    Authors
    Shibata, Takayuki
    Glynn, 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 record
    Abstract
    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 Research
    URI
    http://hdl.handle.net/10541/72793
    http://hdl.handle.net/10541/72774
    DOI
    10.1093/nar/gkl117
    PubMed ID
    16609128
    Type
    Article
    Language
    en
    ISSN
    1362-4962
    ae974a485f413a2113503eed53cd6c53
    10.1093/nar/gkl117
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research
    All Paterson Institute for Cancer Research

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