Selective and Catalytic Conversion of Hydroxymethyl Cytosine to Formyl Cytosine by a Synthetic Model of TET Enzymes

Abstract

The TET enzymes, known as the ten-eleven translocation enzymes, have become central figures in epigenetic regulation due to their remarkable ability to oxidize 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), 5-carboxy cytosine (5-caC) thus influencing gene expression and DNA methylation patterns. Understanding the intricate mechanisms underlying TET enzyme function is crucial for unraveling epigenetic regulatory pathways and their implications in various biological processes, including development, differentiation, and disease progression. Recently, we have shown that FeIIITAML complex acts as a synthetic model of TET enzyme by selectively oxidizing 5-hmC to 5-fC. Herein we report another synthetic model, FeIIIbTAML, for selective and catalytic oxidation of 5-hmC. The current synthetic model overcomes several limitations of the previous TET model reported by us. In addition to oxidizing simple nucleobase, we have shown that the FeIIIbTAML, in the presence of H2O2, can selectively oxidize nucleoside and small DNA fragments containing 5-hmC in a catalytic manner.