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N6mdAChemRXiV.pdf (17.34 MB)
Selective Chemical Functionalization at N6 mdA Residues in DNA
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 21.09.2020 and posted on 22.09.2020by Manuel Nappi, Alexander Hofer, Shankar Balasubramanian, Matthew Gaunt
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