Abdu, K., Aiertza, M.K., Wilkinson, O.J. et al. (5 more authors) (2020) Synthesis of oligodeoxyribonucleotides containing a tricyclic thio analogue of O6-methylguanine and their recognition by MGMT and Atl1. Nucleosides, Nucleotides & Nucleic Acids, 39 (8). pp. 1108-1121. ISSN 1525-7770
Abstract
Promutagenic O6-alkylguanine adducts in DNA are repaired in humans by O6-methylguanine-DNA-methyltransferase (MGMT) in an irreversible reaction. Here we describe the synthesis of a phosphoramidite that allows the preparation of oligodeoxyribonucleotides (ODNs) containing a novel tricyclic thio analogue of O6-methylguanine in which the third ring bridges the 6-thio group and C7 of a 7-deazapurine. These ODNs are very poor substrates for MGMT and poorly recognised by the alkyltransferase-like protein, Atl1. Examination of the active sites of both MGMT and Atl1 suggest large steric clashes hindering binding of the analogue. Such analogues, if mutagenic, are likely to be highly toxic.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Author(s). Published with license by Taylor and Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Tricyclic; O6-methylguanine; oligodeoxyribonucleotide; MGMT; alkyltransferase-like protein |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/R018251/1 ROYAL SOCIETY RGS\R2\180405 BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/T008032/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Jun 2020 15:24 |
Last Modified: | 16 Nov 2021 15:26 |
Status: | Published |
Publisher: | Informa UK Limited |
Refereed: | Yes |
Identification Number: | 10.1080/15257770.2020.1764971 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:161269 |