THESIS
2017
xv, 71 pages : illustrations (some color) ; 30 cm
Abstract
The rationales that researchers utilize today for functional peptide design are mostly
derived from the natural protein and peptide investigations. Indeed, some naturally occurring
peptides can be pathology related. In Alzheimer’s disease, there is a critical motif LVFFA (Aβ
17-
21) in the amyloid-beta (Aβ) peptide, which is responsible for peptide monomer self-assembly
to form oligomers and fibrils. A previous report about peptide and plasmid DNA co-assembly
for gene delivery has made use of this segment, Aβ
17-21 to design a peptide/plasmid
nanostructure. However, putatively, Aβ
17-21 in that peptide has caused the peptide/plasmid
particle to form an overly robust structure and incapacitated gene release and expression. In this
report, the focus is therefore put on controlling th...[
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The rationales that researchers utilize today for functional peptide design are mostly
derived from the natural protein and peptide investigations. Indeed, some naturally occurring
peptides can be pathology related. In Alzheimer’s disease, there is a critical motif LVFFA (Aβ
17-
21) in the amyloid-beta (Aβ) peptide, which is responsible for peptide monomer self-assembly
to form oligomers and fibrils. A previous report about peptide and plasmid DNA co-assembly
for gene delivery has made use of this segment, Aβ
17-21 to design a peptide/plasmid
nanostructure. However, putatively, Aβ
17-21 in that peptide has caused the peptide/plasmid
particle to form an overly robust structure and incapacitated gene release and expression. In this
report, the focus is therefore put on controlling the fibrillation behavior of the Aβ
17-21 modulated
self-assembling peptide. Aβ
17-21, apart from its strongly associative structure, is relatively
insensitive to pH. Therefore, we incorporated the self-assembling motif with pH-sensitive
histidine. Results showed that with histidine-substitution, the fibrillation propensity and
structural robustness of peptide assembly are lowered and the pH-sensitivity is higher.
Meanwhile, bifurcation characteristics and fibrillar height range are retained due to the
sequence similarity. In addition, ultrasound was applied to accelerate both fibril formation and
disruption at different pH conditions. The accelerative effect can act as a compensation for the
slowed fibrillation process. The findings have given an insight into the natural peptide motif
mutation study, demonstrating that the peptide functionality can be adjusted and desired triggers
can be incorporated.
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