A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA

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Abstract

The bifunctional platinum compound, [{trans-PtCl(NH3)2}2 (H2N(CH2)4NH2)]2+, forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N7 positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G4 residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin–DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.

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