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Growth Factor Delivery From Fibrin Matrics Containing Affinity-Based Delivery Systems To Treat Peripheral Nerve Injury, Matthew Wood
Growth Factor Delivery From Fibrin Matrics Containing Affinity-Based Delivery Systems To Treat Peripheral Nerve Injury, Matthew Wood
All Theses and Dissertations (ETDs)
This thesis work sought to develop a biomaterial to further the understanding of affinity-based delivery and to serve as a potential treatment for peripheral nerve injury. The use of an affinity-based delivery system: ABDS) with growth factors in a nerve guidance conduit: NGC) was hypothesized to promote nerve regeneration and functional recovery following a critical nerve defect. Evaluation of affinity-based delivery using peptides with varying binding affinity for heparin determined that peptide binding affinity for heparin affected the release rate and biological activity of nerve growth factor: NGF) in vitro. The ABDS presented biologically active NGF, which promoted neurite extension …
Evaluation Of Pbr In Breast Cancer, Stephany Shockley
Evaluation Of Pbr In Breast Cancer, Stephany Shockley
All Theses and Dissertations (ETDs)
The utility of Positron Emission Tomography: PET) in the detection of cancer began with the radiopharmaceutical 2-[18F]fluoro-2-deoxyglucose: FDG) used for measuring altered cellular metabolism. Specific radioligands are being developed to allow non-invasive analysis of protein expression to further characterize tumors. One protein that has been identified as a promising target is the Peripheral Benzodiazepine Receptor: PBR). PBR expression is up-regulated in several cancers, and in many there has been a correlation drawn between increased malignancy and protein expression levels. Therefore, developing PET methodologies to apply for PBR imaging could be an important step in understanding individual tumors as we move …
Discovery Of Inactive E* Conformations In Thrombin And Other Vitamin K- Dependent Clotting Proteases, Alaji Bah
Discovery Of Inactive E* Conformations In Thrombin And Other Vitamin K- Dependent Clotting Proteases, Alaji Bah
All Theses and Dissertations (ETDs)
Serine proteases of the chymotrypsin family play important roles in the regulation and function of numerous biological processes including digestion, blood coagulation, fibrinolysis, development, fertilization, apoptosis and immunity. For many of these proteases, activity unfolds when a zymogen is activated by limited proteolysis and the associated conformational changes result in the formation of a proper active site and oxyanion hole, both of which are required for efficient hydrolysis of peptide bonds. The transition from zymogen to active enzyme, E, thus provides critical temporal and spatial regulatory mechanism of protease function. Catalytic activity of serine proteases belonging to Vitamin K-dependent clotting …
An Investigation Of Acetobacter Aceti N5-Carboxyaminoimidazole Ribonucleotide Mutase And Its Pure-Purk Operon, Charles Constantine
An Investigation Of Acetobacter Aceti N5-Carboxyaminoimidazole Ribonucleotide Mutase And Its Pure-Purk Operon, Charles Constantine
All Theses and Dissertations (ETDs)
Acetobacter aceti oxidizes ethanol to acetic acid. While the membrane-permeable acetic acid is toxic to many bacteria, A. aceti survives exposure to acetic acid by tolerating cytoplasmic acidification. The ability to tolerate an acidic cytoplasm suggests that proteins from A. aceti are unusually suited to function in an acidic environment. The ability to tolerate an acidic cytoplasm raises additional questions about biosynthetic pathways that employ acid-labile intermediates. To examine how A. aceti metabolism may have adapted to function under acidic conditions, a biosynthetic conversion involving an acid-labile metabolite has been selected for study. The enzyme N5-carboxyaminoimidazole ribonucleotide mutase: PurE) catalyzes …
Accurate Docking Is Achieved By Decoupling Systematic Sampling From Scoring, Jianwen Feng
Accurate Docking Is Achieved By Decoupling Systematic Sampling From Scoring, Jianwen Feng
All Theses and Dissertations (ETDs)
This dissertation discusses two main projects from my thesis work. The first project focuses on the development of a small molecule docking program, SKATE, for drug discovery. The second project focuses on the critical analysis of the thermal stability of a mini-protein, FSD-1. SKATE is a novel approach to small molecule docking. It removes any inter-dependence between sampling and scoring to improve docking accuracy. SKATE systematically and exhaustively samples a ligand's conformational, rotational and translational degrees of freedom, as constrained by a receptor pocket, to find sterically allowed poses. A total of 266 ligands were re-docked to their respective receptors …
Structually Diverse Cu-64-Labeled Rgd Peptide Conjugates For Pet Imaging Of Αvβ3 Expression, Ashley Fiamengo
Structually Diverse Cu-64-Labeled Rgd Peptide Conjugates For Pet Imaging Of Αvβ3 Expression, Ashley Fiamengo
All Theses and Dissertations (ETDs)
Radiolabeled receptor-binding peptides have emerged as an important class of radiopharmaceuticals for diagnostic imaging and cancer therapy. Following radionuclide labeling, the specific receptor-binding properties of the ligand can be exploited to guide the radioactivity to tissues expressing a particular receptor. This dissertation reports on the development of integrin αvβ3-targeting radiopharmaceuticals for medical imaging applications from the perspective of both the radiometal-labeled chelator as well as the targeting peptide. Several macrocyclic copper(II) chelators have been studied with the goal of improving kinetic and in vivo stability. Structurally diverse bifunctional RGD: arginine-glycine-aspartic acid) peptides were investigated for α …
Discovery Of A Novel Metalloregular Family: Structure/Function Studies Of E. Coli Rcnr, Jeffrey Iwig
Discovery Of A Novel Metalloregular Family: Structure/Function Studies Of E. Coli Rcnr, Jeffrey Iwig
All Theses and Dissertations (ETDs)
The first row transition metal ions- Mn, Fe, Co, Ni, Cu and Zn are vital cofactors for proteins involved in diverse processes including photosynthesis, oxidative respiration and protein translation. Despite these essential functions, excess metal ions can lead to cell death through the generation of oxidative damage or the occupation of non-native metal sites. Acquiring metal ions from the environment while limiting possible toxic effects requires the coordinated regulation of metal uptake, trafficking and efflux, which in bacteria is often carried out by metal-responsive transcription factors: metalloregulators). Nickel homeostasis in E. coli is an ideal model system for understanding the …
Computational And Experimental Investigation Of Allosteric Communication In The Transcriptional Regulator Nikr, Michael Bradley
Computational And Experimental Investigation Of Allosteric Communication In The Transcriptional Regulator Nikr, Michael Bradley
All Theses and Dissertations (ETDs)
The Ni2+ and DNA binding protein NikR is involved in nickel regulation in Escherichia coli through transcriptional repression of the NikABCDE nickel permease. NikR is a homotetramer and each chain contains both a DNA binding ribbon-helix-helix: RHH) domain and a Ni2+ binding regulatory ACT: aspartokinase, chorismate mutase, TyrA) fold. Work herein combines computational modeling of NikR structure with experimental studies aimed at understanding allosteric communication between the ACT and RHH domains. Hydrogen/deuterium exchange mass spectrometry shows a Ni2+ specific NikR conformational change relative to bound Cu2+, Co2+, and Zn2+. Concurrent coordination geometry and in vivo repressor function studies show that …
Characterization Of Ligand-Induced Conformational Changes In The Egf Receptor, Katherine Yang
Characterization Of Ligand-Induced Conformational Changes In The Egf Receptor, Katherine Yang
All Theses and Dissertations (ETDs)
ABSTRACT OF DISSERTATION Characterization of ligand-induced conformational changes in the EGF receptor by Katherine S. Yang Doctor of Philosophy in Biochemistry Washington University in St. Louis, 2009 Professor Linda Pike, Chairperson The epidermal growth factor: EGF) receptor is a classical receptor tyrosine kinase that mediates cellular processes such as proliferation, migration, and differentiation in response to growth factor stimulation. Crystal structures of the EGF receptor suggest that its activation is associated with extensive conformational changes in both the extracellular and intracellular domains. However, evidence of these structural dynamics in intact cells has been lacking. This thesis describes the characterization of …
The Evolution And Regulation Of Dna-Binding By The Nickel-Dependent Transcription Factor Nikr, Erin Benanti
The Evolution And Regulation Of Dna-Binding By The Nickel-Dependent Transcription Factor Nikr, Erin Benanti
All Theses and Dissertations (ETDs)
Transition metal homeostasis is critical for all cells to balance cellular metal requirements with metal availability. One common homeostatic mechanism in bacteria is metal-dependent transcriptional regulation. The Ni2+-dependent transcription factor NikR is a member of the ribbon-helix-helix: RHH) family of DNA-binding proteins and is widespread among bacteria and archea with vastly different nickel physiologies. The goal of this thesis was to better understand basic aspects of cellular transition metal homeostasis by examining the activity and regulatory properties of NikR family members from different bacterial species. One organism that exhibits a prominent and well-defined nickel physiology is Helicobacter pylori, making it …