Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
Molecules. 2024 May 11;29(10):2270. doi: 10.3390/molecules29102270.
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.
DNA 不断受到各种内外因素的损害。特别是，氧化损伤处于稳定状态，而 8-氧-2'-脱氧鸟苷（oxodG）被认为是主要的氧化损伤。oxodG 是一种强遗传毒性核苷，被认为与癌症和神经疾病的发病机制有关。然而，尚未开发出检测 DNA 中 oxodG 位置的突破性方法。因此，我们试图使用人工核苷开发一种检测 DNA 中 oxodG 的新方法。最近，我们成功地通过基于嘌呤骨架的核苷衍生物的单核苷酸延伸反应识别了 DNA 中的 oxodG，该衍生物具有 1,3-二氮杂苯并恶嗪单元。在这项研究中，我们开发了一种具有嘧啶骨架的新核苷衍生物，以进一步提高识别能力和酶反应效率。因此，我们设计并合成了 2'-脱氧胞苷-1,3-二氮杂苯并恶嗪（Cdap）及其三磷酸酯衍生物。结果表明，由于其胞嘧啶骨架，它相对于 dG 模板掺入到引物链中，但在 oxodG 模板的互补位置更有效。这些结果表明，这种新的核苷衍生物可以被认为是检测 DNA 中 oxodG 的新候选物之一。
