Nici, Fabrizia (2016) Studies on oligonucleotides and analogues: from drug candidates to components for high-ordered supramolecular structures. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Studies on oligonucleotides and analogues: from drug candidates to components for high-ordered supramolecular structures
Creators:
CreatorsEmail
Nici, Fabriziafabrizia.nici@unina.it
Date: 29 March 2016
Number of Pages: 139
Institution: Università degli Studi di Napoli Federico II
Department: Farmacia
Scuola di dottorato: Biotecnologie
Dottorato: Scienze biotecnologiche
Ciclo di dottorato: 28
Coordinatore del Corso di dottorato:
nomeemail
Sannia, Giovannigiovanni.sannia@unina.it
Tutor:
nomeemail
Oliviero, GiorgiaUNSPECIFIED
Piccialli, GennaroUNSPECIFIED
Date: 29 March 2016
Number of Pages: 139
Uncontrolled Keywords: Oligonucleotides, aptamers, G-Quadruplexes, biochips, PNA
Settori scientifico-disciplinari del MIUR: Area 03 - Scienze chimiche > CHIM/06 - Chimica organica
Date Deposited: 13 Apr 2016 08:44
Last Modified: 31 Oct 2016 13:53
URI: http://www.fedoa.unina.it/id/eprint/10788

Abstract

Last century advances in molecular biology and biotechnologies enabled us to understand the exceptionally broad repertoire of nucleic acids functions. For a long time DNA was regarded as a rigid molecule with the sole purpose to store and transmit genetic information. However, this idea has been completely overtaken with the discovery of the catalytic activity of specific RNA molecules. In effect, the early 1970s and the embryonic works on antisense oligonucleotides paved the way for our current understanding and use of oligonucleotides (ONs) and their analogues in numerous and very different application fields, such as gene modulation, i.e. the antisense and antigene strategies, new generation drugs, i.e. the aptamers, but also nanotechnologies. My research activity is included in this general context and, in particular, has been devoted to unravelling ON uses in a broad range of fields, which goes from the development of novel drug candidates to gene regulation and implementation of new approaches for the simple construction of biosensors. Specifically, my search has been focused on: i) Realization of novel antiviral aptamers and consolidation of a new, cost effective and quick binding assay for the optimization of already reported aptamers, not achievable through the universally accepted method for the individuation of selective and efficient aptamers, the SELEX method; ii) Studies on already reported protocols for the functionalization of Porous Silicon (PSi) matrices, in view of the development of optical DNA-based biosensor and discovery of a new efficient protocol for the PSi-friendly in situ oligonucleotide synthesis; iii) Chemical synthesis and structural and biological characterization of PNA sequences for the inhibition of a miRNA, designated as responsible for the downregulation of the Cystic Fibrosis disease-gene. The achievement of these goals required a combination of chemical synthesis, with the optimization of existing protocols, and techniques for the biophysical and biological characterization of our biomolecules.

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