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Molecules ; 29(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38792131

RESUMO

DNA is constantly damaged by various external and internal factors. In particular, oxidative damage occurs in a steady state, and 8-oxo-2'-deoxyguanosine (oxodG) is known as the main oxidative damage. OxodG is a strong genotoxic nucleoside and is thought to be involved in the pathogenesis of cancer and neurological diseases. However, a breakthrough method to detect the position of oxodG in DNA has not yet been developed. Therefore, we attempted to develop a novel method to detect oxodG in DNA using artificial nucleosides. Recently, we have succeeded in the recognition of oxodG in DNA by a single nucleotide elongation reaction using nucleoside derivatives based on a purine skeleton with a 1,3-diazaphenoxazine unit. In this study, we developed a new nucleoside derivative with a pyrimidine skeleton in order to further improve the recognition ability and enzymatic reaction efficiency. We, therefore, designed and synthesized 2'-deoxycytidine-1,3-diazaphenoxazine (Cdap) and its triphosphate derivatives. The results showed that it was incorporated into the primer strand relative to the dG template because of its cytidine skeleton, but it was more effective at the complementary position of the oxodG template. These results indicate that the new nucleoside derivative can be considered as one of the new candidates for the detection of oxodG in DNA.


Assuntos
8-Hidroxi-2'-Desoxiguanosina , DNA , Desoxicitidina , Oxazinas , DNA/química , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Oxazinas/química , Desoxiguanosina/química , Desoxiguanosina/análogos & derivados , Dano ao DNA , Nucleotídeos/química , Polifosfatos
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