Emendato, Alessandro (2017) Structures and interactions of amyloidogenic polypeptides in biomimetic environments. [Tesi di dottorato]
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| Item Type: | Tesi di dottorato |
|---|---|
| Resource language: | English |
| Title: | Structures and interactions of amyloidogenic polypeptides in biomimetic environments. |
| Creators: | Creators Email Emendato, Alessandro alessandro.emendato@unina.it |
| Date: | 10 April 2017 |
| Number of Pages: | 141 |
| Institution: | Università degli Studi di Napoli Federico II |
| Department: | Scienze Chimiche |
| Dottorato: | Scienze chimiche |
| Ciclo di dottorato: | 29 |
| Coordinatore del Corso di dottorato: | nome email Paduano, Luigi luigi.paduano@unina.it |
| Tutor: | nome email Delia, Picone UNSPECIFIED |
| Date: | 10 April 2017 |
| Number of Pages: | 141 |
| Keywords: | Amyloid, Biophysics, Protein Aggregation |
| Settori scientifico-disciplinari del MIUR: | Area 03 - Scienze chimiche > CHIM/03 - Chimica generale e inorganica |
| Date Deposited: | 03 May 2017 17:23 |
| Last Modified: | 14 Mar 2018 10:03 |
| URI: | http://www.fedoa.unina.it/id/eprint/11740 |
| DOI: | 10.6093/UNINA/FEDOA/11740 |
Collection description
This thesis aims to provide structural and biophysical insights on the molecular mechanism of amyloid aggregation. Three different molecular models were chosen for these studies; all of them being able to form fibrillar aggregates, even though starting from different conformation, therefore likely following different mechanisms. The main model is represented by amyloid beta peptides, in particular the 40 and the 42 residues peptides (Abeta40 and Abeta42), which are related to Alzheimer Disease. The ability to switch from alfa-helical conformation in membrane and apolar environment to beta-sheet-based fibril structure in aqueous solution characterizes these peptides. The second model is hemopressin, a short peptide that shows very promising pharmacological application, hampered by its aggregation propensity; this peptide is unstructured in aqueous buffers, but it forms amyloid fibrils in some pH conditions. The third model is an engineered protein, called Y65R-MNEI, derived from monellin, very interesting for its potential biotechnological application as ipocaloric sweetener. Its structures is very close to that of the parent protein MNEI which, at native state, is a soluble globular protein rich in beta-sheet. Like MNEI, it is able to form fibrils, and may represent a useful model for protein folding and aggregation. Still no aggregation study was performed on Y65R-MNEI. These molecules were studied at different levels of deepness in literature, with several different biophysical techniques. Therefore, the choice of these molecules allowed me to study the amyloid aggregation process at different stages. In particular, the effect of different physico-chemical parameters (temperature, ionic strength, pH and solvent polarity), as well as the influence of lipid interaction and of a non-enzymatic post-translational modification on the aggregation properties of these models was investigated. An integrated experimental approach was used, including biophysical techniques such as Fluorescence, CD, EPR, NMR spectroscopies and AFM, in order to fill some gaps present in literature on the aggregation process of these molecules.
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