TET-Like Oxidation in 5-Methylcytosine and Derivatives: A Computational and Experimental Study.

ABSTRACT: The epigenetic marker 5-methylcytosine (5mC) is an important factor in DNA modification and epigenetics. It can be modified through a three-step oxidation performed by ten-eleven-translocation (TET) enzymes and we have previously reported that the iron(IV)-oxo complex [Fe(O)(Py₅ Me₂ H)]²⁺ (1) can oxidize 5mC. Here, we report the reactivity of this iron(IV)-oxo complex towards a wider scope of methylated cytosine and uracil derivatives relevant for synthetic DNA applications, such as 1-methylcytosine (1mC), 5-methyl-iso-cytosine (5miC) and thymine (T/5mU). The observed kinetic parameters are corroborated by calculation of the C-H bond energies at the reactive sites which was found to be an efficient tool for reaction rate prediction of 1 towards methylated DNA bases. We identified oxidation products of methylated cytosine derivatives using HPLC-MS and GC-MS. Thereby, we shed light on the impact of the methyl group position and resulting C-H bond dissociation energies on reactivity towards TET-like oxidation.

SUBMITTER: Jonasson NSW 

PROVIDER: S-EPMC9293240 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature