Martino, Luigi (2009) DNA QUADRUPLEXES AND PROTEINS: STRUCTURE, STABILITY AND THEIR INTERACTIONS WITH PHARMACOLOGICALLY RELEVANT MOLECULES. [Tesi di dottorato] (Inedito)

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Abstract

In the first part of the thesis my efforts have been focused on the interactions between the DNA quadruplex structures and drugs such as distamycin A and cationic porphyrin. Those drug are able to bind to the quadruplex structure via to completely different binding mode. The distamycin A is a well-know groove binder on the other hand the cationic porphyrin prefers stacking-mode interacting mechanisms. For the previous reasons those molecules are a good starting point, as molecular scaffold, for further chemical optimisations that could enhance their affinity for the quadruplex structures. In a second stage of my PhD studies, I had the possibility to move to the lab of Dr. Maria R Conte at the King’s College of London to further my understanding of protein NMR. In this stimulating environment I started to study the structure and the interaction of the protein SlyD from E.coli. This system represented the possibility to apply all my biophysical skills to the field of the proteins. In my thesis work I faced the study of three different systems, with increasing complexity. All the interactions, that have been characterised, are biological relevant and the study intends to illuminate on their structural and energetic aspects in order to get a deeper understanding of their regulating mechanisms.

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