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合成含β-dA损伤的DNA以探究人跨损伤聚合酶的复制能力。

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

作者信息

Bagale Siddharam Shivappa, Deshmukh Priyanka U, Mandal Soumyadeep, Malvi Harshada, Kondabagil Kiran, Pradeepkumar P I

机构信息

Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

出版信息

J Org Chem. 2025 Jan 17;90(2):1159-1166. doi: 10.1021/acs.joc.4c01683. Epub 2025 Jan 3.

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 -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.

摘要

由链烯基苯天然产物黄樟素(SF)和甲基丁香酚(MEG)形成的DNA加合物主要归因于它们已报道的致癌特性。在此,我们报告了一种简洁的策略来获得 -Ac-SF/MEG-dA亚磷酰胺,它们通过固相DNA合成被选择性地掺入DNA寡核苷酸中。使用人聚合酶hpolκ和hpolη进行的复制研究表明,这两种聚合酶都能无错误地复制这些加合物,这表明这些聚合酶不会导致加合物诱导的致突变性。

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