Synthesis of N6-dA Damaged DNAs to Probe the Replication Ability of Human Translesion Polymerases

IF 3.6 2区 化学 Q1 CHEMISTRY, ORGANIC Journal of Organic Chemistry Pub Date : 2025-01-03 DOI:10.1021/acs.joc.4c01683
Siddharam Shivappa Bagale, Priyanka U. Deshmukh, Soumyadeep Mandal, Harshada Malvi, Kiran Kondabagil, P. I. Pradeepkumar
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Abstract

The DNA adducts formed by the alkenylbenzene natural products, safrole (SF) and methyleugenol (MEG) are primarily attributed to their reported carcinogenic properties. Herein, we report a concise strategy to access N6-Ac-SF/MEG-dA phosphoramidites, which were selectively incorporated into DNA oligonucleotides by solid-phase DNA synthesis. The replication studies using human polymerases hpolκ and hpolη showed that both polymerases replicate these adducts error-free, which indicates that these polymerases do not contribute to the adduct-induced mutagenicity.

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N6-dA损伤dna的合成探讨人类翻译聚合酶的复制能力
由烯基苯天然产物,黄樟酚(SF)和甲基丁香酚(MEG)形成的DNA加合物主要归因于它们报道的致癌特性。在此,我们报告了一种简明的策略来获取N6-Ac-SF/MEG-dA磷酰胺,这些磷酰胺通过固相DNA合成选择性地结合到DNA寡核苷酸中。利用人聚合酶hpolκ和hpolη进行的复制研究表明,这两种聚合酶都能无差错地复制这些加合物,这表明这些聚合酶与加合物诱导的诱变性无关。
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来源期刊
Journal of Organic Chemistry
Journal of Organic Chemistry 化学-有机化学
CiteScore
6.20
自引率
11.10%
发文量
1467
审稿时长
2 months
期刊介绍: Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.
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