Chemistry of the 8‐Nitroguanine DNA Lesion: Reactivity, Labelling and Repair



Alexander, Katie J, McConville, Matthew, Williams, Kathryn R, Luzyanin, Konstantin V ORCID: 0000-0001-9312-7139, O'Neil, Ian A and Cosstick, Richard ORCID: 0000-0002-8687-1071
(2018) Chemistry of the 8‐Nitroguanine DNA Lesion: Reactivity, Labelling and Repair. Chemistry: A European Journal, 24 (12). 3013 - 3020.

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Abstract

The 8-nitroguanine lesion in DNA is increasingly associated with inflammation-related carcinogenesis, whereas the same modification on guanosine 3',5'-cyclic monophosphate generates a second messenger in NO-mediated signal transduction. Very little is known about the chemistry of 8-nitroguanine nucleotides, despite the fact that their biological effects are closely linked to their chemical properties. To this end, a selection of chemical reactions have been performed on 8-nitroguanine nucleosides and oligodeoxynucleotides. Reactions with alkylating reagents reveal how the 8-nitro substituent affects the reactivity of the purine ring, by significantly decreasing the reactivity of the N2 position, whilst the relative reactivity at N1 appears to be enhanced. Interestingly, the displacement of the nitro group with thiols results in an efficient and specific method of labelling this lesion and is demonstrated in oligodeoxynucleotides. Additionally, the repair of this lesion is also shown to be a chemically feasible reaction through a reductive denitration with a hydride source.

Item Type: Article
Uncontrolled Keywords: biological chemistry, DNA lesion, DNA modification, guanine, oligonucleotides
Depositing User: Symplectic Admin
Date Deposited: 11 Jan 2018 14:02
Last Modified: 16 Sep 2021 23:11
DOI: 10.1002/chem.201705541
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3015861