SITE-SPECIFIC AND PHOTOINDUCED ALKYLATION OF DNA BY A DIMETHYLANTHRAQUINONE-OLIGODEOXYNUCLEOTIDE CONJUGATE

A dialkyl-substituted anthraquinone derivative was synthesized and lig ated to a sequence-directing oligodeoxynucleotide to examine its effic iency 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, a s 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 dup lex formed by association of the target and probe. A specificity of C > T > A approximate to G was determined for modification at this posit ion. The overall site and nucleotide selectivity seems to originate fr om the chemical requirements of cross-linking and does not likely refl ect the dominant solution structure of the complex prior to irradiatio n.