EDTA— DNA-binder Complexes

One of the first systems described was Complex (10) which contains the intercalator methidium (MPE—Fe). Indeed, this complex and the tethered complex of Pt to acridine orange are formally analogous as they contain DNA—binder (intercalator) linked to a metal function (Pt—purine binding Fe—radical production). In the presence of micromolar concentrations of Fe, dithiothreitol (DTT) as reducing agent, and in the presence 

These innovative molecules can be of great use as probes of DNA structure and as artificial or synthetic restriction endonucleases by cutting at very specific sites. The cleavage of chromatin and the mapping of antibiotic sites are just some of the uses explored for these complexes [154, 159—161]. Thus, the preferential binding of the antibiotic netropsin to restriction fragments was shown to be at AT-rich regions. 

The antitumour activity of antibiotics, which may act by strand breakage through radical production from a metal-centered redox reaction, will be summarized in Chapter 7. The examples summarized here show the feasibility of design and use of a DNA-binding ligand (ranging from very simple to a molecular weight of 600) to deliver a metal to DNA, where 

Strand breakage, either single strand or double strand, may be effected by metal complexes which are capable of undergoing redox reactions. Reduction of the metal complex, subsequent reaction of the reduced species to produce active oxygen moieties has been demonstrated to produce strand breaks. Photolytic reduction of the complex can also result in strand cleavage. 

The role of DNA in the transmission of genetic information makes it a primary target of drug action. The many metal binding modes on DNA vary widely in their ability to affect DNA synthesis but the variety of binding modes presents considerable scope for design of more efficient agents. 

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