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Biomimetic Iron Complex Achieves TET Enzyme Reactivity*.

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)(Py₅ Me₂ H)]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.

SUBMITTER: Schmidl D

PROVIDER: S-EPMC8518650 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Biomimetic Iron Complex Achieves TET Enzyme Reactivity*.

Schmidl David D Jonasson Niko S W NSW Korytiaková Eva E Carell Thomas T Daumann Lena J LJ

Angewandte Chemie (International ed. in English) 20210820 39

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 [FeIV (O)(Py5 Me2 H)]2+ (1) can serve as a biomimetic model for TET by oxidizing the ...[more]

PMID: 34181314

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