Date of Award

8-31-2014

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Marianna Török

Second Advisor

Béla Török

Third Advisor

Michelle Foster

Abstract

Amyloidoses is a group of human diseases characterized by harmful accumulation of misfolded protein aggregates, rich in β-sheet structures referred as amyloids. Alzheimer's disease (AD), the most common neurodegenerative disease, associated with the misfolding of a small peptide called amyloid-beta (Aβ) is often considered to be the archetype of amyloidosis. Several small molecule inhibitors of Aβ self-assembly, that reduce the production of the amyloidogenic form of proteins or increase their clearance rate have been suggested as an attempt to treat amyloidoses.

In the present work we investigated the impact of small organic molecules on self-assembly of Aβ by biochemical, biophysical and imaging techniques. Chalcones and coumarins, diarylhydrazones, phenylhydrazines and carbonyl compounds were selected based on the analysis of literature information on inhibitors of amyloid formation. We further extended our study to investigate the impact of these small molecules on the fibril formation of hen egg white lysozyme (HEWL) to observe if the effect of these compounds displays any similar trends in two distinct amyloidogenic systems.

Our results indicated that these small molecules have significant impact on the self-assembly of Aβ. We have identified new compounds that have resulted in significant decrease in the fibril formation of Aβ. Our preliminary investigations with HEWL suggest that the molecular probes showed similar inhibitory effect on the fibrillogenesis of lysozyme.

Comments

Free and open access to this Campus Access Thesis is made available to the UMass Boston community by ScholarWorks at UMass Boston. Those not on campus and those without a Healey Library (UMass Boston) barcode may gain access to this thesis through resources like Proquest Dissertations & Theses Global. If you have a Healey Library barcode and would like to download this work from off-campus, click on the "Off-Campus UMass Boston Users" link above.

Share

COinS