TARGET-PROMOTED ALKYLATION OF DNA

Inducible and selective alkylation of DNA was accomplished under neutr al conditions by use of a silyl-protected phenol that served as a prec ursor for a highly reactive quinone methide. As expected, addition of fluoride triggered reaction of a model compound, methylsiloxy)-4-[(p-n itrophenoxy)methyl]benzamide, and its oligodeoxynucleotide conjugate. Surprisingly, the silyl phenol was also specifically yet more slowly a ctivated by the environment of duplex DNA in the absence of fluoride. This alternative process was associated with the hybridization of prob e and target strands, and single-stranded DNA was unable to induce a s imilar activation. Therefore, DNA appears to effect its own alkylation by promoting the formation of an electrophilic and nondiffusible inte rmediate.