Reversible Alkylation of DNA by Quinone Methide Bioconjugates

The N7 of dG is one of the most nucleophilic sites within duplex DNA and is relatively accessible within the major groove.59 However, QM-dependent alkylation 

1 The Reversibility of Quinone Methide Reaction Does Not Preclude Its Use in Forming DNA Cross-Links 

SCHEME 9.16 DNA cross-linking by tandem quinone methide formation. 

The reversibility of DNA cross-linking by the QMPs illustrated in Fig. 9.4 has not been examined directly but is presumably controlled as before by the leaving group strength of the DNA nucleophiles and the electronic characteristics of the QM intermediates. Unless both possible QMs form simultaneously, the cross-linking agents still remain bound to DNA at one site as the other is transiently released during 

FIGURE 9.4 Representative quinone methide precursors for DNA cross-linking.61 66 

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