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postgraduate thesis: Amphiphilic peptides containing alternating α-aminoxy acids and α-amino acids to mimic the α-helix of bak BH3 domain and disulfide bondas covalent linkage for stabilizing 7/8 helix
Title | Amphiphilic peptides containing alternating α-aminoxy acids and α-amino acids to mimic the α-helix of bak BH3 domain and disulfide bondas covalent linkage for stabilizing 7/8 helix |
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Authors | |
Issue Date | 2011 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Zhang, T. [张婷]. (2011). Amphiphilic peptides containing alternating α-aminoxy acids and α-amino acids to mimic the α-helix of bak BH3 domain and disulfide bond as covalent linkage for stabilizing 7/8 helix. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4786940 |
Abstract | The binding between the survival protein Bcl-xL and the death-promoting region of
the Bcl-2-related protein Bak is one of the key protein-protein interactions in the
regulation of programmed cell death (apoptosis). Since it is well recognized that the
BH3 domain of Bak adopts an amphipathic α-helix to interact with Bcl-xL through
hydrophobic and electrostatic effects, conformational studies and possible
applications of the α-aminoxy acid-containing peptides as mimics of the α-helix of
Bak BH3 domain have been carried out. The main results are summarized below.
Four short peptides ZT1?ZT4 containing alternating α-aminoxy acids/α-amino acids
as the mimics of the α-helix of Bak protein were designed and synthesized. However,
none of these four peptides, at the concentration of 25 μM, exhibited a significant
inhibitory effect on the Bcl-xL inhibition test. Circular dichroism spectroscopic
studies on ZT1?ZT4 as well as short model peptides N-minus, N-plus, C-minus and
C-plus suggest that the proposed secondary structure, the 7/8 helix, is not stable in
aqueous solutions.
1H NMR, 2D NMR and circular dichroism spectroscopic studies on the disulfide
bond-constrained short peptides 4.7?4.9 with alternating α-aminoxy acids and
α-amino acids suggest that a disulfide linker with three methylene units between
adjacent α-amino acid residues could dramatically increase the stability of the 7/8
helix even in a mixed buffer/methanol solution.
1H NMR, 2D NMR and circular dichroism spectroscopic studies have also revealed
that the hybrid soluble peptides C-free, N-free and Both-free containing α-amino
acids and β-2,2-cyclopropyl-amino acids adopted a stable 8/8 helix in aqueous
solution. |
Degree | Doctor of Philosophy |
Subject | Peptides - Synthesis. Anions. Amino acids. Oligomers. |
Dept/Program | Chemistry |
Persistent Identifier | http://hdl.handle.net/10722/183043 |
HKU Library Item ID | b4786940 |
DC Field | Value | Language |
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dc.contributor.author | Zhang, Ting | - |
dc.contributor.author | 张婷 | - |
dc.date.accessioned | 2013-05-05T03:00:16Z | - |
dc.date.available | 2013-05-05T03:00:16Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Zhang, T. [张婷]. (2011). Amphiphilic peptides containing alternating α-aminoxy acids and α-amino acids to mimic the α-helix of bak BH3 domain and disulfide bond as covalent linkage for stabilizing 7/8 helix. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4786940 | - |
dc.identifier.uri | http://hdl.handle.net/10722/183043 | - |
dc.description.abstract | The binding between the survival protein Bcl-xL and the death-promoting region of the Bcl-2-related protein Bak is one of the key protein-protein interactions in the regulation of programmed cell death (apoptosis). Since it is well recognized that the BH3 domain of Bak adopts an amphipathic α-helix to interact with Bcl-xL through hydrophobic and electrostatic effects, conformational studies and possible applications of the α-aminoxy acid-containing peptides as mimics of the α-helix of Bak BH3 domain have been carried out. The main results are summarized below. Four short peptides ZT1?ZT4 containing alternating α-aminoxy acids/α-amino acids as the mimics of the α-helix of Bak protein were designed and synthesized. However, none of these four peptides, at the concentration of 25 μM, exhibited a significant inhibitory effect on the Bcl-xL inhibition test. Circular dichroism spectroscopic studies on ZT1?ZT4 as well as short model peptides N-minus, N-plus, C-minus and C-plus suggest that the proposed secondary structure, the 7/8 helix, is not stable in aqueous solutions. 1H NMR, 2D NMR and circular dichroism spectroscopic studies on the disulfide bond-constrained short peptides 4.7?4.9 with alternating α-aminoxy acids and α-amino acids suggest that a disulfide linker with three methylene units between adjacent α-amino acid residues could dramatically increase the stability of the 7/8 helix even in a mixed buffer/methanol solution. 1H NMR, 2D NMR and circular dichroism spectroscopic studies have also revealed that the hybrid soluble peptides C-free, N-free and Both-free containing α-amino acids and β-2,2-cyclopropyl-amino acids adopted a stable 8/8 helix in aqueous solution. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.source.uri | http://hub.hku.hk/bib/B47869409 | - |
dc.subject.lcsh | Peptides - Synthesis. | - |
dc.subject.lcsh | Anions. | - |
dc.subject.lcsh | Amino acids. | - |
dc.subject.lcsh | Oligomers. | - |
dc.title | Amphiphilic peptides containing alternating α-aminoxy acids and α-amino acids to mimic the α-helix of bak BH3 domain and disulfide bondas covalent linkage for stabilizing 7/8 helix | - |
dc.type | PG_Thesis | - |
dc.identifier.hkul | b4786940 | - |
dc.description.thesisname | Doctor of Philosophy | - |
dc.description.thesislevel | Doctoral | - |
dc.description.thesisdiscipline | Chemistry | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_b4786940 | - |
dc.date.hkucongregation | 2012 | - |
dc.identifier.mmsid | 991033514949703414 | - |