Selective Chemical Functionalization at N6 mdA Residues in DNA

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-adenosine–an epigenetic modification of emerging importance. A carefully orchestrated reaction combines reduction of a nitropyridine to form a nitrosopyridine spin-trapping reagent and an exquisitely selective tertiary aminemediated hydrogen-atom abstraction at the N6-methyl group to form an a-amino radical. Cross-coupling of the putative a-amino radical with nitrosopyridine leads to a stable conjugate, installing a label at N6- methyl-adenosine. We show that N6-methyl-adenosine-containing oligonucleotides can be enriched from complex mixtures, paving the way for applications to identify this modification in genomic DNA and RNA