Skip Navigation

Nucleic Acids Research 2006 34(6):1884-1891; doi:10.1093/nar/gkl117
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (200K) Freely available
Right arrow Screen PDF (209K) Freely available
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Shibata, T.
Right arrow Articles by Williams, D. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shibata, T.
Right arrow Articles by Williams, D. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 11 April 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Article

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

Takayuki Shibata1, Nicola Glynn2, T. Brian H. McMurry3, R. Stanley McElhinney3, Geoffrey P. Margison2 and David M. Williams1,*

1 Department of Chemistry, Centre for Chemical Biology Richard Roberts Building, University of Sheffield Sheffield, S3 7HF, UK 2 Cancer Research-UK Carcinogenesis Group, Paterson Institute for Cancer Research Manchester, M20 4BX, UK 3 University Chemical Laboratory, Trinity College Dublin 2, Ireland

*To whom correspondence should be addressed. Tel: +44 114 222 9502; Fax: +44 114 222 9346; Email: d.m.williams{at}sheffield.ac.uk

Received December 2, 2005. Revised January 10, 2006. Accepted March 12, 2006.

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
S. J. Pearson, S. Wharton, A. J. Watson, G. Begum, A. Butt, N. Glynn, D. M. Williams, T. Shibata, M. F. Santibanez-Koref, and G. P. Margison
A novel DNA damage recognition protein in Schizosaccharomyces pombe.
Nucleic Acids Res., January 1, 2006; 34(8): 2347 - 2354.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.