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The Role Of Gln146 To The Stability And Activity Of Manganese Superoxide Dismutase, Ting Wang Jan 2017

The Role Of Gln146 To The Stability And Activity Of Manganese Superoxide Dismutase, Ting Wang

Theses and Dissertations--Chemistry

Gln146 is a highly conserved outer-sphere amino acid residue at the active site of MnSOD. It serves as a hydrogen bond donor to both the solvent molecules at the active site and Tyr 34, the conserved “gateway” amino acid residue. This dissertation develops our understanding of the effect of amino acid Gln146 at the second shell of the active site of metalloprotein MnSOD in facilitating metal binding, the modulation of redox potential, and the optimization of catalytic activity and structure stability. Different from the wild-type MnSOD, Q146E is always purified as a completely apo-protein with zero active metal ion and …


Oxidative Stress And Proteomic Studies Of Mammalian Models Of Age-Related Metabolic Dysfunction In Neurodegenerative Disorders, Aaron M. Swomley Jan 2017

Oxidative Stress And Proteomic Studies Of Mammalian Models Of Age-Related Metabolic Dysfunction In Neurodegenerative Disorders, Aaron M. Swomley

Theses and Dissertations--Chemistry

Expression proteomics is the field of science wherein proteins that make up the cellular proteome are identified both by name and by fold-change. Depending on the application of proteomics, this change in level could be due to internal cellular stressors or introduction of xenobiotics. Global oxidative stress measures use immunohistochemistry to determine the relative level of oxidative stress of macromolecules within the cell. In this dissertation, both global oxidative stress measures and expression proteomics were used in a variety of mammalian models in order to determine the effects of protein upregulation, intranasal insulin administration, and resveratrol supplementation on the cellular …


Illuminate The Pathway Of Membrane Protein Association And Degradation, Zhaoshuai Wang Jan 2017

Illuminate The Pathway Of Membrane Protein Association And Degradation, Zhaoshuai Wang

Theses and Dissertations--Chemistry

Escherichia coli transporter protein AcrB and its homologues are the inner membrane components of the Resistance-Nodulation-Division (RND) family efflux pumps in Gram-negative bacteria. It is well accepted that soluble proteins are only marginally stable, but such insight is missing for membrane proteins. The lack of stability data, including thermodynamic stability and oligomer association affinity is a result of intrinsic difficulties in working with membrane proteins. In addition, the degradation of soluble proteins in E. coli has been extensively studied whereas the degradation process of membrane proteins remains unclear. A focus of my thesis is the validation and development of methods …


Synthesis And Development Of Zwitterionic Pei (Zpei) For Optimized Delivery Of Nucleic Acids, Joseph Raleigh Duke Iii Jan 2017

Synthesis And Development Of Zwitterionic Pei (Zpei) For Optimized Delivery Of Nucleic Acids, Joseph Raleigh Duke Iii

Theses and Dissertations--Chemistry

Gene therapy holds promise for the treatment a wide range of diseases ranging from cystic fibrosis to cardiovascular disease to cancer. The need for safe and efficient gene delivery methods remains the primary barrier to human gene therapy. Non-viral vector materials, including polymers, can be designed to be biocompatible and non-immunogenic, but lack the efficiency to be clinically relevant. Gene therapy awaits the development of new materials that are both safe and efficient. Here, we have synthesized a series of modified zwitterionic polymers based on the common transfecting agent polyethylenimine (PEI). Using a variety of biochemical and biophysical methods we …