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

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