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Mechanistic Studies on RNA Strand Scission from a C2'-Radical.

ABSTRACT: The C2'-carbon-hydrogen bond in ribonucleotides is significantly weaker than other carbohydrate carbon-hydrogen bonds in RNA or DNA. Independent generation of the C2'-uridine radical (1) in RNA oligonucleotides via Norrish type I photocleavage of a ketone-substituted nucleotide yields direct strand breaks via cleavage of the ?-phosphate. The reactivity of 1 in different sequences and under a variety of conditions suggests that the rate constant for strand scission is significantly greater than 106 s-1 at pH 7.2. The initially formed C2'-radical (1) is not trapped under a variety of conditions, consistent with computational studies ( Chem.-Eur. J. 2009 , 15 , 2394 ) that suggest that the barrier to strand scission is very low and that synchronous proton transfer from the 2'-hydroxyl to the departing phosphate group facilitates cleavage. The C2'-radical could be a significant contributor to RNA strand scission by the hydroxyl radical, particularly under anaerobic conditions where 1 can be produced from nucleobase radicals.

SUBMITTER: Paul R

PROVIDER: S-EPMC5055465 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Mechanistic Studies on RNA Strand Scission from a C2'-Radical.

Paul Rakesh R Greenberg Marc M MM

The Journal of organic chemistry 20160926 19

The C2'-carbon-hydrogen bond in ribonucleotides is significantly weaker than other carbohydrate carbon-hydrogen bonds in RNA or DNA. Independent generation of the C2'-uridine radical (1) in RNA oligonucleotides via Norrish type I photocleavage of a ketone-substituted nucleotide yields direct strand breaks via cleavage of the β-phosphate. The reactivity of 1 in different sequences and under a variety of conditions suggests that the rate constant for strand scission is significantly greater than 1 ...[more]

PMID: 27668445

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