Selective Chemical Functionalization at N6-Methyladenosine Residues in DNA Enabled by Visible-Light-Mediated Photoredox Catalysis.

ABSTRACT: Selective chemistry that modifies the structure of DNA and RNA is essential to understanding the role of epigenetic modifications. We report a visible-light-activated photocatalytic process that introduces a covalent modification at a C(sp³)-H bond in the methyl group of N6-methyl deoxyadenosine and N6-methyl adenosine, epigenetic modifications of emerging importance. A carefully orchestrated reaction combines reduction of a nitropyridine to form a nitrosopyridine spin-trapping reagent and an exquisitely selective tertiary amine-mediated hydrogen-atom abstraction at the N6-methyl group to form an ?-amino radical. Cross-coupling of the putative ?-amino radical with nitrosopyridine leads to a stable conjugate, installing a label at N6-methyl-adenosine. We show that N6-methyl deoxyadenosine-containing oligonucleotides can be enriched from complex mixtures, paving the way for applications to identify this modification in genomic DNA and RNA.

SUBMITTER: Nappi M 

PROVIDER: S-EPMC7760100 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature