Photochemical control of DNA structure through radical disproportionation.
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--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.
Department of Chemistry, The Johns Hopkins University, 138 Remsen Hall, 3400 N. Charles Street, Baltimore, MD 21218 (USA).
Joanna Maria N
JM
San Pedro
Marc M
MM
Greenberg
D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D021881:DNA, Catalytic / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation; D055668:Photochemical Processes; D013936:Thymidine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism
D021881:DNA, Catalytic; D005609:Free Radicals; D004247:DNA; D013936:Thymidine
DNA modification; modified oligonucleotides; nucleic acid modifying enzymes; photochemical control