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Review
. 2004 Oct;98(10):1578-84.
doi: 10.1016/j.jinorgbio.2004.04.021.

Potential adenine and minor groove binding platinum complexes

Affiliations
Review

Potential adenine and minor groove binding platinum complexes

J Grant Collins et al. J Inorg Biochem. 2004 Oct.

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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