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  • Title: Potential adenine and minor groove binding platinum complexes.
    Author: Grant Collins J, Wheate NJ.
    Journal: J Inorg Biochem; 2004 Oct; 98(10):1578-84. PubMed ID: 15458819.
    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(NH(3))(2)](2)mu-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.
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