The aim of this dissertation was 1) to explore early stage aggregation kinetic
behavior of Amyloid-β 1-40 (Aβ1-40) by incorporation of unnatural amino acid pcyanophenylalanine
as a site-specific fluorescence reporter, 2) to explore the effect of
macromolecules on the aggregation of Aβ1-40.
Chapter One provides an introduction of Alzheimer’s disease as an amyloidogenic
disease, amyloidogenic peptide and amyloid formation. Details were shown about the
research progress of Aβ1-40 aggregation and Aβ1-40’s interaction with polyelectrolytes,
and how treatments studies were designed.
In Chapter two, using Aβ1-23 as a model molecule, the distinct site-specific
dynamics was identified, during amyloid formation, and the structural characteristics of
amyloid fibrils were defined by using an unnatural amino acid, p-cyanophenylalanine, as
a sensitive fluorescent and Raman probe. The results reveal distinct local environmental changes of specific residues during the aggregation of Aβ1-23. The results also suggest
that an edge-to-face aromatic interaction between the F4 and F19 residues from the
adjacent in-register β-strands plays a key role in the conformational conversion to form
and stabilize β-sheet structure.
In Chapter Three, p-cyanophenylalanine was incorporated in the full sequence of
Aβ1-40. Site-specific information from p-cyanophenylalanine fluorescence was studied
and summarized.
In Chapter Four, the inhibiting effect of an anionic polyelectrolyte poly(4-
styrenesulfonate) (PSS) on the aggregation of Aβ1-40 peptide was reported. The results
demonstrate the strong inhibition potential of PSS on the aggregation of Aβ1-40.
Additional studies indicate that the presence of both aliphatic backbone as well as
aromatic side chain group in PSS is essential for its inhibition activity.
In Chapter Five, it was investigated the effect of two polyelectrolytes, chitosan
(CHT) and N-trimethyl chitosan chloride (TMC), on the aggregation of Aβ1-40. Results
show that both CHT and TMC exhibit a concentration-dependent decrease of amyloid
aggregation suggesting their application as amyloid assembly inhibitors. Their binding
mechanism was investigated by computational modeling which shows that Aβ1-40
monomer was primarily stabilized by electrostatic interactions with charged amine and
quaternary amines of CHT and TMC respectively.
Chapter Six, describes all experimental procedures and instrument setup in detail. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection
| Identifer | oai:union.ndltd.org:fau.edu/oai:fau.digital.flvc.org:fau_33934 |
| Contributors | Liu, Haiyang (author), Du, Deguo (Thesis advisor), Florida Atlantic University (Degree grantor), Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry |
| Publisher | Florida Atlantic University |
| Source Sets | Florida Atlantic University |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation, Text |
| Format | 155 p., application/pdf |
| Rights | Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder., http://rightsstatements.org/vocab/InC/1.0/ |
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