Potential adenine and minor groove binding platinum complexes

J. Grant Collins, Nial J. Wheate

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

This paper is a focused review of our recent efforts to produce multi-nuclear platinum anti-cancer complexes that preferentially target adenine residues in DNA. Multi-nuclear platinum complexes, like cisplatin, predominantly form covalent adducts with guanine bases; however, controlling the pre-covalent binding association of the metal complex may modify this preference. NMR experiments, using oligonucleotides, indicate that multi-nuclear complexes linked by flexible diaminoalkanes will pre-associate in the DNA minor groove at A/T rich regions. Despite this pre-covalent binding preference, these complexes still predominantly covalently bind guanine residues. However, using 4,4′-dipyrazolylmethane (dpzm) as a linking ligand produces a dinuclear platinum complex, trans-[{PtCl(NH3)2}2μ-dpzm]2+, that covalently binds DNA with a preference for adenine bases. In vitro transcription assays also demonstrate that the dpzm-based complex covalently binds within an A/T rich region of the 512 base-pair segment of DNA used for the study.
Original languageEnglish
Pages (from-to)1578-1584
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume98
Issue number10
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

Keywords

  • Adenine adducts
  • Anti-cancer
  • Dinuclear platinum(II) complex
  • Minor groove binding

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