Site-specific and photo-induced alkylation of DNA by a dimethylanthraquinone-oligodeoxynucleotide conjugate.
A dialkyl-substituted anthraquinone derivative was synthesized and ligated to a sequence-directing oligodeoxynucleotide to examine its efficiency and specificity for cross-linking to complementary sequences of DNA. The anthraquinone appendage stabilized spontaneous hybridization of the target and probe sequences through non-covalent interactions, as indicated by thermal denaturation studies. Covalent modification of the target was induced by exposure to near UV light (lambda > 335 nm) to generate cross-linked duplexes in yields as great as 45%. Reaction was dependent on the first unpaired nucleotide extended beyond the duplex formed by association of the target and probe. A specificity of C > T > A = G was determined for modification at this position. The overall site and nucleotide selectivity seems to originate from the chemical requirements of cross-linking and does not likely reflect the dominant solution structure of the complex prior to irradiation.
Kang
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Department of Chemistry, State University of New York at Stony Brook, 11794, USA.
Rokita
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D000478:Alkylation; D000880:Anthraquinones / Q000138:chemical synthesis / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000138:chemical synthesis / Q000378:metabolism*; D018983:DNA Footprinting; D004591:Electrophoresis, Polyacrylamide Gel; D017665:Hydroxyl Radical / Q000378:metabolism; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides; D010787:Photosensitivity Disorders; D014466:Ultraviolet Rays
D000880:Anthraquinones; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D017665:Hydroxyl Radical; D004247:DNA