Photochemical Control of DNA Structure through Radical Disproportionation

Authors

  • Joanna Maria N. San Pedro,

    1. Department of Chemistry, The Johns Hopkins University, 138 Remsen Hall, 3400 N. Charles Street, Baltimore, MD 21218 (USA)
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  • Prof. Dr. Marc M. Greenberg

    Corresponding author
    1. Department of Chemistry, The Johns Hopkins University, 138 Remsen Hall, 3400 N. Charles Street, Baltimore, MD 21218 (USA)
    • Department of Chemistry, The Johns Hopkins University, 138 Remsen Hall, 3400 N. Charles Street, Baltimore, MD 21218 (USA)===

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Abstract

Photolysis of an aryl sulfide-containing 5,6-dihydropyrimidine (1) at 350 nm produces high yields of thymidine and products resulting from trapping of a 5,6-dihydrothymidin-5-yl radical by O2 or thiols. Thymidine is believed to result from disproportionation of the radical pair originally generated from C[BOND]S bond homolysis of 1 on the microsecond timescale, which is significantly shorter than other photochemical transformations of modified nucleotides into their native forms. Duplex DNA containing 1 is destabilized, presumably due to disruption of π-stacking. Incorporation of 1 within the binding site of the restriction endonuclease EcoRV provides a photochemical switch for turning on the enzyme's activity. In contrast, 1 is a substrate for endonuclease VIII and serves as a photochemical off switch for this base excision repair enzyme. Modification 1 also modulates the activity of the 10–23 DNAzyme, despite its incorporation into a nonduplex region. Overall, dihydropyrimidine 1 shows promise as a tool to provide spatiotemporal control over DNA structure on the miscrosecond timescale.

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