Sequence-specificity for DNA interstrand cross-linking by α,ω-alkanediol dimethylsulfonate esters:: Evidence for DNA distortion by the initial monofunctional lesion

The sequence specificity for DNA cross-linking by a series of alpha,omega-alkanediol dimethylsulfonate esters (CH3SO2O-(CH2)(n)-OSO2CH3) is described. The results show that bifunctional alkylating agents that produce 5- and 6-carbon interstrand linkages (n = 5 and 6) prefer to react at N7-guanine at 5'-GNC sires. When n = 8, a more random cross-linking pattern is observed at 5'-GNC and S'-GC. As previously reported with the nitrogen mustard bis(2-chloroethyl)methylamine (mechlorethamine), the predominant site of crosslinking at 5'-GNC by the n = 5 compound is not consistent with the distance between the N7-G sites in B-DNA and the length of the covalent linkage.