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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

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Academic year: 2021

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Preface

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Preface

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 (Reddy et al., 1999). Many efforts have been devoted in recent years 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.

The isoquinoline alkaloids constitute an important class of natural products endowed with extensive biological applications (Bhakuni and Jain, 1986). They are widely distributed in several botanic families. The most important member of this group is berberine and its synthetic analogue coralyne (here investigated), both of them being promising antitumor agents with low citotoxicity.

Acridines were the first chromophores whose non covalent interactions with DNA were extensively studied and now their binding to double strands is almost universally interpreted according to intercalation (Lerman, 1961; Aggarwal et al., 1984; Adams, 2002; Malinina et al., 2002; Biver et al., 2003). They are a special class of compounds, showing interesting chemical and physical properties, widely investigated owing to their potential as chemotherapeutic drugs and their large use in the pharmaceutical and dye industries (Zittoun, 1985; Adams, 2002).

Cyanines are molecules commonly used as selective staining agents for the analysis of nucleic acids and proteins in gel and capillary electrophoresis (Haugland, 1996).

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Preface

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In this PhD thesis a chapter is devoted to each of the investigated nucleic acid/dye systems. Since some data treatments are in common to the different systems, repetitions could be found when these can help the reader to better understand how the results have been obtained.

The derivation of the equations, related to the mathematical methods employed for the analysis of the data, can be found in the Appendices at the end of the thesis.

Some of the results obtained have been either published in Journals or presented in Meetings and Congresses as reported in the Publications list at the end of this thesis.

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