File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleAmphiphilic 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
Authors
Issue Date2011
PublisherThe 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
AbstractThe 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.
DegreeDoctor of Philosophy
SubjectPeptides - Synthesis.
Anions.
Amino acids.
Oligomers.
Dept/ProgramChemistry
Persistent Identifierhttp://hdl.handle.net/10722/183043

 

DC FieldValueLanguage
dc.contributor.authorZhang, Ting-
dc.contributor.author张婷-
dc.date.accessioned2013-05-05T03:00:16Z-
dc.date.available2013-05-05T03:00:16Z-
dc.date.issued2011-
dc.identifier.citationZhang, 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.urihttp://hdl.handle.net/10722/183043-
dc.description.abstractThe 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.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B47869409-
dc.subject.lcshPeptides - Synthesis.-
dc.subject.lcshAnions.-
dc.subject.lcshAmino acids.-
dc.subject.lcshOligomers.-
dc.titleAmphiphilic 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.typePG_Thesis-
dc.identifier.hkulb4786940-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineChemistry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4786940-
dc.date.hkucongregation2012-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats