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

Danzhou Yang, Stella S.G.E. van Boom, Jan Reedijk, Jacques H. van Boom, Nicholas Farrell, Andrew H.J. Wang

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

The bifunctional platinum compound, [{trans-PtCI(NH3)2}2(H2N(CH2)4NH2)]2+f 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.

Original languageEnglish (US)
Pages (from-to)577-586
Number of pages10
JournalNature Structural Biology
Volume2
Issue number7
DOIs
StatePublished - Jul 1995

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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