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

2.50
Hdl Handle:
http://hdl.handle.net/10541/72774
Title:
Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT).
Authors:
Shibata, Takayuki; Glynn, Nicola; McMurry, T Brian H; McElhinney, R Stanley; Margison, Geoffrey P; Williams, David M
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.
Affiliation:
Department of Chemistry, Centre for Chemical Biology, Richard Roberts Building, University of Sheffield, Sheffield, S3 7HF, UK.
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
Issue Date:
2006
URI:
http://hdl.handle.net/10541/72774; http://hdl.handle.net/10541/72793
DOI:
10.1093/nar/gkl117
PubMed ID:
16609128
Type:
Article
Language:
en
ISSN:
1362-4962
Appears in Collections:
All Paterson Institute for Cancer Research; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorShibata, Takayuki-
dc.contributor.authorGlynn, Nicola-
dc.contributor.authorMcMurry, T Brian H-
dc.contributor.authorMcElhinney, R Stanley-
dc.contributor.authorMargison, Geoffrey P-
dc.contributor.authorWilliams, David M-
dc.date.accessioned2009-07-07T12:08:46Z-
dc.date.accessioned2009-07-07T12:08:47Z-
dc.date.available2009-07-07T12:08:47Z-
dc.date.available2009-07-07T12:08:46Z-
dc.date.issued2006-
dc.identifier.citationNovel 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.en
dc.identifier.issn1362-4962-
dc.identifier.pmid16609128-
dc.identifier.doi10.1093/nar/gkl117-
dc.identifier.urihttp://hdl.handle.net/10541/72774-
dc.identifier.urihttp://hdl.handle.net/10541/72793-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshOligodeoxyribonucleotides-
dc.subject.meshOrganophosphorus Compounds-
dc.titleNovel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT).en
dc.typeArticleen
dc.contributor.departmentDepartment of Chemistry, Centre for Chemical Biology, Richard Roberts Building, University of Sheffield, Sheffield, S3 7HF, UK.en
dc.identifier.journalNucleic Acids Researchen
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.