On the folding and conformation of peptides and the development of novel methods for their study [electronic resource].

Waegele, Matthias M.
400 p.
Chemistry, Physical and theoretical.
Local subjects:
Penn dissertations -- Chemistry. (search)
Chemistry -- Penn dissertations. (search)
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Mode of access: World Wide Web.
Proteins are polymers, whose complex chemistry and physics, in the course of evolution, permitted their recruitment for immensely diverse functions in the biological machinery. Therefore, the study of protein conformational behavior and interactions of proteins with other entities of the intra- and extra-cellular milieu is of great interest. In this Thesis, we do not only quantitatively study the folding of peptide and protein systems using well-established spectroscopic techniques, but also, in recognizing the limits of existing experimental techniques, develop novel methods for studying protein folding, protein-protein and protein-membrane interactions.
In the first part of this Thesis, we are concerned with studying the folding process under various conditions using small peptides or proteins as model systems that allow a tractable, quantitative description of the order-disorder transition. Employing a combined site-directed mutagenesis/temperature-jump kinetics approach, we elucidated the folding mechanism of a helical hairpin, which is an important intermediate in protein folding reactions. We further considered how the folding kinetics of such model peptides and proteins are altered in the presence of high concentrations of macromolecular cosolutes, which are thought to provide a simplified model system for the interior of the cellular environment. In another study, we addressed current questions concerning the structural properties of the unfolded state ensemble using a polypeptide that is unstructured by design as a model system.
The second part of this Thesis is focused on the development of novel methods to study both protein folding and interactions of proteins with other molecular species. In recent years, the nitrile stretching bands of nitrile-derivatized amino acid side-chains have emerged as attractive probes for monitoring biomolecular processes. In this Thesis, we theoretically and experimentally studied the molecular determinants of the bandwidth of the nitrile stretching band of 5-cyanotryptophan. We further evaluated the feasibility of using light-induced reductive cleavage of disulfide bonds as a means to phototrigger protein folding reactions.
Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 2011.
Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: .
Adviser: Feng Gai.
Local notes:
School code: 0175.
Gai, Feng, advisor
University of Pennsylvania.
Contained In:
Dissertation Abstracts International 73-03B.
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Restricted for use by site license.
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