Esposito Veronica

Biography

1996: Classic Maturity Diploma (vote 60/60) 2001 : Ph.D. in Pharmaceutical Chemistry and Technology, University of Naples "Federico II" (vote: 110/110 and praise); experimental thesis in Organic Chemistry: "H NMR study of the interaction of distamycin A and netropsin with sequence d (TGGGGT) in quadruplex structure"; Speaker: Prof. Luciano Mayol 2004 : PhD in "Medicine Science"; XVII cycle, Department of Chemistry of Natural Substances, Faculty of Pharmacy, University of Naples "Federico II"; tutor: Prof. Luciano Mayol, titled "Synthesis and Structural Characterization of Oligonucleotides and Analogues Able to Form Quadruplex Structures".

Research Interest

Dr. Esposito's research activity focuses mainly on the design, synthesis and structural characterization of analogous oligodeoxyribonucleotides forming G-quadruplex structures. Quadruplex are unusual secondary DNA structures, adopted by sequences rich in guanine, whose biological importance depends on their presence in different regions of the human genome, such as the promoter regions of several genes, including oncogenes, centromers, and telomeres. Moreover, due to their high thermal stability, G-quadruplex is the predominant structural motif of several aptamers, which are synthetic oligodeoxyribonucleotides, often obtained by SELEX combinatorial technology, with remarkable affinity and selectivity for certain target molecules, both protein and smaller dimensions, and therefore considered potentially very promising therapeutic agents. In this context, the research lines followed are aimed at improving pharmacokinetic and pharmacodynamic properties of oligodeoxyribonucleotides forming quadruplex structures with potential therapeutic activity. To this end, several structural changes have been proposed, especially at the level of the nitrogenous bases or the sugar-phosphate skeleton. Structural modifications of the nitrogen base can favor the assumption of a precise glycosidic conformation by the modified nucleoside which, in turn, is able to influence the relative orientation of the filaments of the quadruplex structure and, therefore, the conformation type adopted. In addition, modified nucleosides, capable of adopting a specific glycosidic conformation, inserted into appropriate positions in certain oligonucleotide sequences can greatly contribute to the stabilization of certain types of quadruplex structures. While base modifications may be able to increase aptamer selectivity by providing further contact with target molecule, sugar-phosphate skeleton modifications may increase their resistance to attack of nucleases, thereby preserving the their functionality in a physiological environment. A research line devoted to this purpose was therefore focused on assessing the ability to form quadruplex structures by sequences containing LNA, PNA, L-nucleotide or 5'-5 'or 3' polarity inversion sites -3 '. The research activity carried out is also focused on designing, synthesis and structural analysis of modified oligonucleotides capable of forming quadruplex structures with the aim of improving the stability and properties of aptamers and of obtaining the most suitable models for structural study and target interaction. These research projects have been based, in particular, on the examination of novel aptamic inhibitors of thrombin and gp120 protein of the HIV-1 virus, and on the interaction study of small molecules with telomeric DNA. For detailed study of the structures adopted by modified synthetic ODNs and target interaction, single- and two-dimensional nuclear magnetic resonance spectroscopy techniques are used. Other techniques, such as circular dichroism, UV spectroscopy and gel electrophoresis, are used for further investigation, in order to evaluate the effect of different modifications on the properties of quadruplex structures. These studies aimed at evaluating the possibility of controlling topology and orientation of filaments, insertion of chemical groups into the grooves and increased stability in the physiological environment of quadruplex complexes, are aimed at the design of synthetic models of quadruplex structures (telomer, c-kit regulators, c-kit, c-myc, k-ras, etc.), which are of utmost importance in the study of the interaction of anti-cancer drugs (both intercalating and binding the pelvis) with quadruplex structures involved in important biological processes.