Insight into macromolecular interactions involving nucleic acids: a study of the interaction of G-quadruplexes with pharmacologically active molecules and investigations of the RNA binding properties of LARP4 protein.

Abstract

This dissertation can be divided in two parts. In the first part, my efforts have been focused on the study of the Gquadruplex structures. In chapter one, I describe the unusual arrangement of the DNA to form the G-quadruplex structures and their biological role, underlying the reason why in the last period a lot of research groups focused their studies on this topic. In chapter two, after a brief introduction of the first molecules capable to bind the G-quadruplex (Distamicyn A and its derivates), I describe the new organic molecule capable to interact with the DNA quadruplex, which I have discovered applying some innovative approaches during my PhD. In the second part of this thesis I introduce the research conducted in the laboratory of Dr. Maria R. Conte at the King’s College of London. In this stimulating environment I started studying the structure of the protein LARP4 and its interaction with a poly (A) RNA using the NMR. In the course of my research I have learnt the techniques allowing to do the transformation, the expression and the purification of the protein. A summary presentation of the techniques I have applied is reported in the second part in chapter five.