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Chemistry of the 8‐Nitroguanine DNA Lesion: Reactivity, Labelling and Repair
Author(s) -
Alexander Katie J.,
McConville Matthew,
Williams Kathryn R.,
Luzyanin Konstantin V.,
O'Neil Ian A.,
Cosstick Richard
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705541
Subject(s) - chemistry , reactivity (psychology) , dna damage , guanosine , labelling , reagent , deoxyguanosine , dna , guanine , alkylation , stereochemistry , nucleotide , biochemistry , combinatorial chemistry , organic chemistry , alternative medicine , pathology , gene , catalysis , medicine
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 N 2 position, whilst the relative reactivity at N 1 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.