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. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/183043 |
| Date | January 2011 |
| Creators | Zhang, Ting, 张婷 |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Source | http://hub.hku.hk/bib/B47869409 |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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