Quadruplex DNA: A Promising Drug Target for the Medicinal Inorganic Chemist

Stephen      F. Ralph

Abstract

Compounds that can bind to and stabilize quadruplex DNA structures in telomeres, or induce formation of such structures from ssDNA, represent an attractive general approach to the treatment of cancer. Until recently most effort in this area has been directed towards the synthesis of organic compounds for this purpose. More recently there has been growing recognition that metal complexes offer a number of potential advantages for the preparation of lead complexes that bind with high affinity and selectivity for quadruplex DNA. This review seeks to discuss the work that has been reported in this area to date. While most early studies focused on metal complexes of porphyrin ligands, during the past 4 years there has been a dramatic increase in the number of papers in the literature examining the potential of mononuclear complexes of a variety of other ligands, particularly Schiff base ligands and those based on phenanthroline, as quadruplex DNA binders and telomerase inhibitors. In addition, there has been growing interest in exploiting supramolecular chemistry to prepare novel multinuclear complexes that bind to this new drug target.

Keywords: Quadruplex DNA, telomerase, metal complex, porphyrin, absorption spectroscopy, qDNA, cancer, G-tetrads, PLATINUM COMPLEXES, FRET analysis, Fibre X-ray diffraction, stacking interactions, Mass spectrometric analysis, Fluorescence Intercalator Displacement (FID) assay, PAGE analysis