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Issue 36, 2010
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Excursions in polynuclear platinum DNA binding

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Abstract

Polynuclear platinum agents are a structurally unique class of anti-cancer drugs, distinct from the cisplatin family. To describe the chemistry and biology of this class, it was necessary to challenge the accepted paradigms for the structure–activity relationships; design new chemotypes and delineate the structures and consequences of their DNA binding modes. This article summarizes the structural changes induced in DNA by both covalent (bond-forming) and non-covalent (ligand recognition) adducts. Solution (Nuclear Magnetic Resonance), solid state (crystallography) and gas-phase (Electrospray Ionization Mass Spectrometry) techniques have all been used to describe the new DNA structures along with molecular biological techniques. The combined approaches allow molecular description of hitherto unobserved adducts such as long-range major-groove interstrand crosslinks; directional isomers on DNA and a third class of ligand–DNA binding, the phosphate clamp. The phosphate recognition is distinct from ‘‘classic’’ minor-groove recognition or intercalation.

Graphical abstract: Excursions in polynuclear platinum DNA binding

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Article information


Submitted
05 May 2010
Accepted
29 Jun 2010
First published
09 Aug 2010

Chem. Commun., 2010,46, 6640-6650
Article type
Feature Article

Excursions in polynuclear platinum DNA binding

J. B. Mangrum and N. P. Farrell, Chem. Commun., 2010, 46, 6640
DOI: 10.1039/C0CC01254H

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