ETD

Archivio digitale delle tesi discusse presso l'Università di Pisa

Tesi etd-12272021-100016


Tipo di tesi
Tesi di laurea magistrale LM5
Autore
GARFAGNINI, IRENE
URN
etd-12272021-100016
Titolo
Study of protein misfolding driving the synthesis of new small molecules inspired by natural compounds
Dipartimento
FARMACIA
Corso di studi
CHIMICA E TECNOLOGIA FARMACEUTICHE
Relatori
relatore Prof.ssa Nencetti, Susanna
Parole chiave
  • Transthyretin
  • Tau protein
  • Neurodegeneration
  • Fibrils Detection
  • Small Molecules Synthesis
  • Protein Misfolding
Data inizio appello
26/01/2022
Consultabilità
Non consultabile
Data di rilascio
26/01/2092
Riassunto
The project of this master thesis was carried on in collaboration with the Department of Pharmacy of Paris-Saclay University.
The work was focused on studying and preventing protein misfolding since it is correlated to neurodegenerative diseases onset and progression. The project was centred on two amyloidogenic proteins: Transthyretin (TTR) responsible of TTR-related amyloidosis (A-TTR), and Tau, one of the proteins involved in Alzheimer’s disease.
During the first three months of my stage in France, I set up some fluorescence assays to evaluate the aggregation of TTR and a fragment of Tau protein in the presence of potential inhibitors, using ThT as fluorescent dye.
In details, I analysed three series of small molecules, belonged to Pisa home-library, on TTR protein. For the most promising compounds I carried out 8-anilino-1-naphtalensulfonic acid (ANS) competitive binding assay to evaluate their IC50.
Moreover, during this period, I synthetised two fragments of Tau protein by solid phase synthesis, and I analysed their aggregation kinetics with ThT. One of them was used to screen some peptido-mimetics present in Paris-Saclay home-library and some ferulic-acid analogues belonged to Pisa home-library.
The promising results obtained on ferulic acid analogues led to the synthesis of new compounds inspired by natural ones. These compounds were prepared coupling some selected natural derivatives with an aromatic ring substituted in o, m, p position with CF3.
The synthesis and characterization of the new derivatives were carried out at Pisa University.
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