Présentation
Binding and cleavage of nucleic acids has recently become important issues in areas of research as anticancer therapeutic intervention and the development of diagnostic structural probes, with huge impact in medicine and biotechnology. Both artificial and natural metallonucleases have an expected ability for interacting with nucleic acids. In general, these molecules bind DNA in a non-covalent interaction fashion and catalyze the hydrolysis of deoxynucleotide phosphates through hydrolytic or oxidative mechanisms. For the synthesized metallonucleases the main problem is the lack of specificity of DNA cleavage. In drug development this aspect can lead to high cytotoxicity and progressively resistance in tumor cells. Despite the progress of recent years in this field there are many questions that remain unexplored. In this context, an experimental set-up based on multidimensional nuclear magnetic resonance (NMR) spectroscopy was chosen to test different metal complexes, particularly the Fe(III)Zn(II) and a series of mono and binuclear Cu(II), in interaction with oligonucleotides of different sizes and structures. The analysis will use additional biophysical techniques and the objective is to investigate some perspectives on site selectivity in these systems. Addressing DNA conformational changes and accomplishing them by thermodynamic approach is an opportunity to study the multipoint interaction of the complexes and measure mechanisms in different substates. The project intends to produce a rich set of data and to model accurate predictions of the essential requirements of an artificial nuclease: high cleavage efficiency, DNA affinity and sequence differentiation.