Department Chemie, Ludwig-Maximilians-University München, Butenandtstr. 5-13, Haus D, München, Germany.
Angew Chem Int Ed Engl. 2021 Sep 20;60(39):21457-21463. doi: 10.1002/anie.202107277. Epub 2021 Aug 20.
The epigenetic marker 5-methyl-2'-deoxycytidine (5mdC) is the most prevalent modification to DNA. It is removed inter alia via an active demethylation pathway: oxidation by Ten-Eleven Translocation 5-methyl cytosine dioxygenase (TET) and subsequent removal via base excision repair or direct demodification. Recently, we have shown that the synthetic iron(IV)-oxo complex [Fe (O)(Py Me H)] (1) can serve as a biomimetic model for TET by oxidizing the nucleobase 5-methyl cytosine (5mC) to its natural metabolites. In this work, we demonstrate that nucleosides and even short oligonucleotide strands can also serve as substrates, using a range of HPLC and MS techniques. We found that the 5-position of 5mC is oxidized preferably by 1, with side reactions occurring only at the strand ends of the used oligonucleotides. A detailed study of the reactivity of 1 towards nucleosides confirms our results; that oxidation of the anomeric center (1') is the most common side reaction.
表观遗传标记 5-甲基-2'-脱氧胞苷（5mdC）是 DNA 中最常见的修饰物。它可以通过一种主动的去甲基化途径被去除，即：TET（Ten-Eleven Translocation 5-甲基胞嘧啶双加氧酶）的氧化作用，随后通过碱基切除修复或直接去修饰作用。最近，我们已经表明，合成的铁（IV）-氧配合物 [Fe（O）（Py Me H）]（1）可以作为 TET 的仿生模型，将碱基 5-甲基胞嘧啶（5mC）氧化为其天然代谢物。在这项工作中，我们使用一系列 HPLC 和 MS 技术证明，核苷甚至短的寡核苷酸链也可以作为底物。我们发现，1 优先氧化 5mC 的 5 位，只有在使用的寡核苷酸链的链端才会发生副反应。对 1 对核苷的反应性的详细研究证实了我们的结果；即，糖苷中心（1'）的氧化是最常见的副反应。
