DNA and RNA Cleavage Mediated by Phenanthroline-Cuprous Oligonucleotides: From Properties to Applications

Abstract

Several metallic ions when bound to a ligand bringing them in close proximity to nucleic acids are able to cleave phosphodiester bonds, in the presence of oxygen. Redox-active iron and copper ions induced DNA cleavage in the presence of bleomycin, a well-known antitumoral antibiotic interacting with DNA double helix. Small molecules such as ethylene-diamine tetraacetic acid (EDTA), porphyrin, and 1,10-phenanthroline (OP) chelate redox-active divalent metal cations to form EDTA-Fe(II), porphyrin-Fe (II), and OP-Cu(I) complexes, and also induce DNA cleavage with production of hydroxyl radicals or metal-oxo derivatives leading to hydroxylation via oxidative insertion of deoxyribose or ribose moieties that in turn leads to cleavage of phosphodiester bonds via a variety of elimination reaction schemes. Since their discoveries, the cleavage properties of these metal complexes have been used in footprinting experiments to analyze the structure of protein-nucleic acid complexes. These cleavage reagents have also been tethered to larger molecules such as oligonucleotides, proteins, and intercalating agents, which confer additional specificity. This review will focus on the 1,1O-phenanthroline- copper complex and its cleavage properties when conjugated to macromolecules, especially in the case of oligonucleotides. For other use of OP-Cu complexes, one can refer to previous reviews (Sigman et al. 1993b; Chen et al. 2001; Hermann and Heumann 2000; Milne et al. 2001; Muth and Hill200l). We present here a few examples of the utilization of these cleaving 1,10-phenanthroline- copper conjugates in biochemical studies as structural probes, as artificial ribo- and deoxyribonucleases and as modulators of gene expression.