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Schmidl, David; Jonasson, Niko S. W.; Korytiakova, Eva; Carell, Thomas und Daumann, Lena J. (2021): Biomimetic Iron Complex Achieves TET Enzyme Reactivity**. In: Angewandte Chemie-International Edition, Bd. 60, Nr. 39: S. 21457-21463

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Abstract

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-IV(O)(Py5Me2H)](2+) (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.

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