Biomimetic Iron Complex Achieves TET Enzyme Reactivity*.
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 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.
['Schmidl|David|D|', 'Jonasson|Niko S W|NSW|', 'Korytiaková|Eva|E|', 'Carell|Thomas|T|', 'Daumann|Lena J|LJ|0000-0003-2197-136X']
D044503:5-Methylcytosine D040761:Biomimetic Materials D049308:Dioxygenases D058085:Iron Compounds D008968:Molecular Conformation
TET enzymes 5-methyl cytosine iron(IV)-oxo DNA methylation bioinorganic chemistry enzyme models