Mechanisms of the Interaction of Fluorescent Dyes with Nucleic Acids

In recent years, increased attention has been focused in the ways in which drugs interact with biological systems, with the goal of understanding the toxic as well as the chemotherapeutic effects of these small molecules. Dyes that non-covalently bind DNA have received considerable attention due to their potential use as antitumour-drugs and as tools to study and visualize DNA. Many efforts have been devoted to find fluorescent dyes which could provide a convenient alternative to the employment of classical ones (acridines, phenanthridines) and recent developments in biochemistry are often concerned with the study of new molecules that are able to bind and react with DNA and whose properties as drugs need to be tested. These new probes can provide a better understanding of the activity of many drugs and anticancer agents and be of help in developing new diagnostic tools. Many molecules containing planar aromatic ring systems can interact with nucleic acids, intercalating between base pairs or fitting into the polynucleotide grooves, these interactions being the basis of subsequent biological activity. The object of this PhD thesis is the study of the interactions of DNAs and RNAs with dyes, belonging to different chemical families, using a mechanistic approach. The interaction processes are investigated by UV-vis and fluorescence spectroscopy and by relaxation methods (T-Jump and/or stopped-flow), under different temperatures and ionic strength conditions. The dyes chosen in this work are small molecules that, although of different chemical constitution, all contain planar aromatic rings as a common feature. Among them an alkaloid, an acridine derivative and cyanines dyes