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DNase I footprinting of cis- or trans-Diamminedichloroplatinum(II)-modified DNA

1994; Elsevier BV; Volume: 236; Issue: 4 Linguagem: Inglês

10.1016/0022-2836(94)90002-7

1089-8638

A. Schwartz, M. Leng,

Ferrocene Chemistry and Applications

DNase I has been used as an enzymatic probe to visualize the conformational alteration induced in DNA by the binding of either the antitumor drug cis-platinum (cis-DDP) or the therapeutically inactive derivatives, trans-platinum (trans-DDP) and chlorodiethylene-triamineplatinum(II) (dien-Pt). We have constructed double-stranded oligonucleotides (52-mer) containing a single adduct either at the d(GG) site (cis-DDP intrastrand cross-link) or at the d(GC/GC) site (cis-DDP interstrand cross-link) or at the d(G/C) site (trans-DDP interstrand cross-link) or at the d(G) site (dien-Pt adduct). The platinated oligonucleotides are differently recognized by DNase I. As judged by DNase I, the distortions induced in the DNA double helix by the cis-DDP and trans-DDP interstrand cross-links spread over more base-pairs than that induced by the cis-DDP intrastrand cross-link.