Physical Sciences and Mathematics Commons^™

Influence Of Cholesterol And Bilayer Asymmetry On Membrane Protein Distribution In Polymer-Tethered Raft-Mimicking Lipid Membranes, Noor Fueza Hussain

Open Access Dissertations

It is now widely recognized that lipid rafts, which are membrane domains enriched in cholesterol (CHOL) and sphingolipids (SL), play a significant functional role in the plasma membrane. Raft domains particularly affect membrane functionality by causing sequestering of membrane proteins. Underlying mechanisms of raft-associated membrane protein sequestration remain elusive, due to the complexity, transient nature, and small size of raft domains in cellular membranes. To address these challenges, this dissertation unveils the relationship between lipid raft composition and membrane protein sequestration and function using raft-mimicking model membrane mixtures comprised of coexisting liquid-ordered (lo) and liquid-disordered (ld) domains with reconstituted membrane …

Design, Synthesis, And Evaluation Of Molecular Inhibitors For Biologically Relevant Enzymes, Sarah Emma St. John

Open Access Dissertations

The work in this thesis details the design, synthesis, and biological evaluation of molecular inhibitors for the inhibition of biologically relevant enzymes. The first three chapters of this thesis concern the polyphenol resveratrol and its inhibition of the quinone reductase 2 (QR2) enzyme. The work on this subject resulted in the complete design, synthesis, biological and structural evaluation of a second generation library of resveratrol analogues. From this work we identified a novel resveratrol analogue that inhibits QR2 in a previously unknown binding orientation. The fourth chapter of this thesis details the de novo design of molecules for the inhibition …

Gas-Phase Covalent And Non-Covalent Ion/Ion Chemistry Of Biological Macromolecules, John Robert Stutzman

Open Access Dissertations

Gas-phase ion/ion chemistry involves the interaction of oppositely charged ions inside of the mass spectrometer. During this gas-phase chemistry, particle transfer (i.e., proton and electron) or synthesis can occur at rapid reaction rates. Particle transfer represents a mature area of ion/ion chemistry, while selective covalent modification represents a fairly new area of gas-phase chemistry. Gas-phase covalent chemistry is based on traditional solution phase organic chemistry.

The work demonstrated in this dissertation greatly involves gas-phase covalent and non-covalent Schiff base chemistry on peptide and protein ions. The reagent dianion, 4-formyl 1,3-benzene disulfonic acid, has been used to covalently modify unprotonated primary …

Biophysical Studies Of Cholesterol In Unsaturated Phospholipid Model Membranes, Justin Adam Williams

Open Access Dissertations

Cellular membranes contain a staggering diversity of lipids. The lipids are heterogeneously distributed to create regions, or domains, whose physical properties differ from the bulk membrane and play an essential role in modulating the function of resident proteins. Many basic questions pertaining to the formation of these lateral assemblies remain. This research employs model membranes of well-defined composition to focus on the potential role of polyunsaturated fatty acids (PUFAs) and their interaction with cholesterol (chol) in restructuring the membrane environment. Omega-3 (n-3) PUFAs are the main bioactive components of fish oil, whose consumption alleviates a variety of health problems by …

Development Of Isotags For Nmr Based Metabolite Profiling And Applications, Fariba Tayyari

Open Access Dissertations

NMR spectroscopy is a powerful analytical tool for both qualitative and quantitative metabolite profiling analysis. However, accurate quantitative analysis of biological systems especially using one dimensional NMR has been challenging due to signal overlap. In contrast, the enhanced resolution and sensitivity offered by chemoselective isotope tags have enabled new and enhanced methods for detecting hundreds of quantifiable metabolites in biofluids using NMR spectroscopy or mass spectrometry. In this thesis we show improved sensitivity and resolution of NMR experiments imparted by 15N and 13C isotope tagging which enables the accurate analysis of plasma metabolites. To date, isotope tagging has been used …

Synthesis Of Novel Isoprenoid Diphosphate Analogs As Chemical Tools To Investigate Protein Geranylgeranylation, Kayla Jo Temple

Open Access Dissertations

Many proteins require prenylation in order to be biologically functional. Some such proteins include the small Ras and Rho GTPase superfamilies, nuclear lamins A and B, and the kinesin motor proteins CENP-E and F. Prenyltransferase (PTase) inhibition is currently being explored as a possible treatment not only for cancer but for a wide variety of other diseases.

Clinical studies revealed that the effectiveness of farnesyltransferase inhibitors (FTIs) to treat Ras-dependent tumors is determined by which isoform of Ras is overactive. Unfortunately the majority of Ras-dependent tumors have a mutation in either the N- or K-Ras isoforms; both of these isoforms …

Generation And Statistical Modeling Of Active Protein Chimeras: A Sequence Based Approach, Nicholas Fico

Open Access Dissertations

Generation of active protein chimeras is a valuable tool to probe the functional space of proteins. Statistical modeling is the next logical step, allowing us to build a model of gene fragment replaceability between species. In this thesis I begin to develop the statistical tools that are needed to systematically describe combinatorial protein libraries. I present three sets of diverse chimeric protein libraries developed using sequence information. The statistical model of the human N-Ras and human K-Ras-4B genes reveal a set previously unidetifed surface residues on the N-Ras G-Domain that may be involved in cellular localization. Statistical modeling of a …

An Analysis Of The Impact Of Storage Temperature, Moisture Content & Duration Upon The Chemical Components & Bioprocessing Of Lignocellulosic Biomass, Arun Athmanathan

Open Access Dissertations

The successful utilization of lignocellulosic biomass as a feedstock for fuels and chemicals necessitates storage for 2-6 months. It is correspondingly important to understand the impact of storage parameters - moisture concentration, temperature and duration - on biomass quality.

As aerobic storage is the most viable large-scale solution, aerobic storage experiments were carried out with three projected bioenergy feedstocks - sweet sorghum (Sorghum bicolor) bagasse, corn (Zea mays) stover and switchgrass (Panicum virgatum). Stored samples of each were examined for dry matter loss and composition change to develop a material balance around carbohydrates and lignin.

A mean dry matter loss …