M. Chatterjee et Se. Rokita, THE ROLE OF A QUINONE METHIDE IN THE SEQUENCE-SPECIFIC ALKYLATION OF DNA, Journal of the American Chemical Society, 116(5), 1994, pp. 1690-1697
Oligonucleotide-naphthoquinone conjugates were prepared and examined f
or use as inducible, site-directed alkylating agents of DNA. Reaction
was found to be sequence specific and under control of either biomimet
ic reduction or near-UV irradiation. Both conditions induced the forma
tion of a transient and highly electrophilic intermediate consistent w
ith a quinone methide. Enzymatic reduction of 5-((mesyloxy) methyl)- a
nd 5-(bromomethyl) naphthoquinone derivatives produced cross-linking b
etween a target and probe sequence, but the equivalent 5-(acetoxymethy
l), 5-(hydroxymethyl) and 5-methyl analogues were predictably inactive
. Conversely, irradiation of the 5-methylnaphthoquinone derivative pro
duced cross-linking through a mechanism of photochemical enolization t
hat was not available to the 6-methyl, 3-methyl, or unsubstituted anal
ogues. Hydroxyl radical footprinting of the modified DNA demonstrated
that guanine and cytosine were targets of alkylation.