Pagano, Alessia
(2018)
Investigating non-canonical nucleic acid structures and their interaction with potential anticancer drugs.
[Tesi di dottorato]
| Item Type: |
Tesi di dottorato
|
| Resource language: |
English |
| Title: |
Investigating non-canonical nucleic acid structures and their interaction with potential anticancer drugs |
| Creators: |
| Creators | Email |
|---|
| Pagano, Alessia | alessia.pagano@unina.it |
|
| Date: |
11 December 2018 |
| Number of Pages: |
248 |
| Institution: |
Università degli Studi di Napoli Federico II |
| Department: |
Farmacia |
| Dottorato: |
Scienza del farmaco |
| Ciclo di dottorato: |
31 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| D'auria, Maria Valeria | madauria@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Pagano, Bruno | UNSPECIFIED |
|
| Date: |
11 December 2018 |
| Number of Pages: |
248 |
| Keywords: |
DNA; Anticancer agents; Medicinal chemistry |
| Settori scientifico-disciplinari del MIUR: |
Area 03 - Scienze chimiche > CHIM/08 - Chimica farmaceutica |
[error in script]
[error in script]
| Date Deposited: |
19 Dec 2018 11:58 |
| Last Modified: |
22 Jun 2020 09:25 |
| URI: |
http://www.fedoa.unina.it/id/eprint/12631 |
Collection description
The outstanding structural polymorphism of DNA allows for the formation of non-canonical secondary structures, such as G-quadruplexes (G4s), G-triplexes (G3s) and i-motifs. G4 and i-motif structures are found within important functional genomic regions such as telomeres and gene promoters. In particular, they are localized within the promoter regions of several proto-oncogenes, whose overexpression leads to malignant transformation, where they play a major role in the regulation of transcription. In many cases, the biological consequence of non-canonical secondary structure formation in the promoter element is gene silencing. For this reason, the search for ligands able to bind and stabilize G4s and/or i-motifs is pharmacologically very important to develop new anticancer strategies.
In this PhD thesis, a series of studies have been carried out with the aim of investigating these non-canonical nucleic acid structures and their interaction with potential anticancer drugs. Such studies have led to the discovery of new and selective G4 ligands (Chapter 3). Chapter 4 deals with the tandem application of virtual screening along with experimental investigations, that led to discover the first dual G-triplex/G-quadruplex stabilizing compound. In Chapter 5, biophysical techniques have been employed to demonstrate that some well-known G4 ligands are also able to interact with i-motif structure.
The last section of this PhD thesis deals with a study conducted in Dr. Vincenzo Abbate’s laboratory at King’s College London (UK). It concerns the design and synthesis of a new class of gallium chelator to be employed in the development of chemically-modified nucleic acid aptamers to be used as theranostics.
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