Target-promoted alkylation of DNA.

Inducible and selective alkylation of DNA was accomplished under neutral conditions by use of a silyl-protected phenol that served as a precursor for a highly reactive quinone methide. As expected, addition of fluoride triggered reaction of a model compound, 3-(tert-butyldimethylsiloxy)-4-[(p-nitrophenoxy)methyl]benzamide, and its oligodeoxynucleotide conjugate. Surprisingly, the silyl phenol was also specifically yet more slowly activated by the environment of duplex DNA in the absence of fluoride. This alternative process was associated with the hybridization of probe and target strands, and single-stranded DNA was unable to induce a similar activation. Therefore, DNA appears to effect its own alkylation by promoting the formation of an electrophilic and nondiffusible intermediate.