Structural investigations on the adducts formed by natural and synthetic compounds with non-canonical DNA foldings

Non-canonical DNA structures are involved in fundamental biological processes as replication, transcription and repair. Their dysregulation is indeed connected to the development of several human diseases, including cancer. As more and more information about their existence and function in living cells are documented, such DNA structures have emerged as promising therapeutic targets. In the last decades, the G-quadruplex folding has caught the attention of scientists because of its implication in the origin and growth of various cancer forms. The stabilization of G-quadruplex structures at human telomeres is thought to be particularly attractive as it might lead to the identification of potential drug candidates with wide-spectrum anticancer activity and reduced side effects in comparison to classical chemotherapies. The research project underlying this thesis concerns the structural investigation on the interaction of non-canonical DNA foldings, especially of the human telomeric G-quadruplex, with natural and synthetic compounds in order to select potential anticancer drugs. The characterization of ligand-DNA adducts has been carried out primarily by X-ray crystallography which provides detailed structural information. In addition, alternative techniques, as CD spectroscopy and in silico calculations, have supplied complementary data with particular reference to the formation of adducts in solution.