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Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 32 for “"Protein scaffold"”.
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Engineering mono- and multi-valent inhibitors on a modular repeat-protein scaffold to target oncogenic Tankyrase
Tandem-repeat proteins are a class of proteins ubiquitous in nature and exploited in recent years in biotechnological and pharmaceutical applications due to their favourable biophysical properties. One such repeat motif, the tetratricopeptide repeat (TPR), has already been exploited for …
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Spectroscopic Characterization of H93G Myoglobin Cavity Mutant As A Versatile Protein Scaffold For Modeling Native Heme Iron Coordination Structures and Investigation of the Structure and Mechanism of the Dual-Function Enzyme, Amphitrite Ornata Dehaloperoxidase
… structure of the heme iron coordination unit in proteins. H93G Mb complexes with different exogenous ligands have been successfully prepared as models for native heme iron active sites ligated by proximal His (imidazole), Lys (amines), seleno-Cys (selenols) and Met (thioethers). Particularly, a …
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Adaptive fabrication of biofunctional decellularized extracellular matrix niche towards complex engineered tissues
… study, I present a biofunctional ECM-mimicking protein scaffold with tunable biochemical, mechanical and topographical properties. This scaffold, formed by microfibres, displays three favorable characteristics as a cell culture platform: high-loading of key ECM proteins, single-layered mesh …
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Development Towards an Ethylene Sensing Artificial Metalloenzyme
… be made biocompatible by encasing it within a protein scaffold making it an artificial metalloenzyme. To this end biotinylated N-heterocyclic carbenes (NHCs) were synthesized, which can be appended onto the ruthenium probe. Efforts towards the expression and purification of the protein scaffold …
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Understanding the Speciation of Ruthenium Arene Complexes as Precursors to Unnatural Enzyme Cofactors
… many potential Lewis basic ligands provided by protein scaffolds. Combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), X-ray crystallography and other biophysical characterisation techniques, the speciation of ruthenium arene bipyridine complexes with small molecule …
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Protein Engineering via in Vitro Coevolution
The creation of novel protein functions represents a significant challenge in protein engineering. To address this challenge, I have developed a simple and efficient method---in vitro coevolution---for the creation of novel protein functions in an existing protein scaffold. The in vitro coevolution …
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Development of Metal-based Nanomaterials for Biomedical Applications
… was developed, where a designed protein scaffold initiates the nucleation and subsequent growth of gold ions. To gain insight into controlling the size and morphology of the synthesized nanoparticles, interactions between the gold ions and the protein surface were studied along …
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Toward Engineering Oxygenase Activity into the Electron Transfer Protein Azurin
… in understanding the function of metalloproteins and is critical to harnessing their power. Modeling within a protein scaffold offers a pathway to the rational design of desired function s by use of Nature’s own tools; both to gain novel insights into metal-mediated processes and to …
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Electric Fields: A Metric for Molecular-level Understanding of Protein Mechanisms
… the molecular mechanisms at the origin of protein function remains a challenge due to the complex non-covalent interactions that shape their structure. Since the non-covalent interactions arise from charge fluctuations, electric fields can be used as a tool to quantify the interactions …
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DESIGNING A PLATFORM FOR DEVELOPING NOVEL GLYCAN-BINDING PROTEINS USING YEAST SURFACE DISPLAY
… reliable reagents. Many existing glycan-binding proteins exhibit broad specificity, low affinity, and are costly to produce. Thus, there is an urgent need for a rapid, high-throughput platform that can produce high-affinity glycan-binding proteins. We discuss the design of one such platform based …
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Modeling the active sites of diiron and dicopper metalloproteins with napthyridine-, phthalazine-, and diethynylbenzene-based ligands
… to mimic this chemistry in the absence of a protein scaffold. In this introductory chapter, a brief overview is presented of ligand systems that have been used to prepare diiron complexes, and the subsequent oxidation chemistry of these systems is outlined. Chapter 2. Carboxylate, …
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New protein engineering approaches for potentiating and studying antibody-based EGFR antagonism
… of the EGF receptor (EGFR), rendering this protein an attractive therapeutic target. Anti-EGFR therapeutics are a mainstay of clinical practice for the treatment of colorectal, lung and head and neck cancers but efficacy is limited and response rates low. Opportunities for improving EGFR …
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Supercharging: An Investigation into the Effects of External Amino Acid Residue Charge on the Solubility and Internal Electric Character of Bound Ligands in a Heme-Binding de novo-Designed Protein
<p>De novo protein design offers many interesting prospects both as a means to better understand natural protein dynamics and as a potential resource in biomedical and industrial applications. In this work I describe the modification of a simple, well-characterized heme-binding protein by altering …
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Metalloprotein Engineering Using Heme Protein Scaffolds to Investigate the Oxidation of Endogenous Aromatic Amino Acids and Exogenous Substrates
Protein engineering by rational design has been used to study heme proteins and artificial Mn-salen containing metalloenzymes using heme protein scaffolds. Heme proteins perform a wide variety of functions including the catalysis of numerous different reactions. Some of the structural features …
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Bio-inspired iron and cobalt complexes featuring a secondary coordination sphere: ligand design, complexation, and modeling of enzymatic processes
… and cellular signaling. Metallocofactors and protein scaffolds often work in conjunction to attract and bind the small molecules, stabilize reactive intermediates, and shuttle protons and electrons to and from the active site. However, due to the size and dynamic nature of the protein scaffold …
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Rational Design and Application of Antibodies for Amylin and Amyloid Beta
Misfolded proteins and polypeptides such as amylin (islet amyloid polypeptide, IAPP) and amyloid beta are associated with numerous age-related pathological conditions such as Alzheimer's, Parkinson's, and type II diabetes, but effective treatments for these diseases are currently lacking. …
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Hierarchical protein assemblies with biomedical applications
… materials are generated. Among these processes, protein self-assembly into hierarchical structures provides an important avenue for the development of materials with a wide range of biomedical applications. Self-assembly exploits the formation of strong, non-covalent interactions between …
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Changes in the Oligodendrocyte Progenitor Cell Nuclear Lamina During Ageing
… role of the nuclear lamina (a nucleoplasmic protein scaffold) in the functional response of OPCs to the mechanical properties of their microenvironment. Work in this thesis identified changes in the expression levels of the nuclear lamina proteins Lamin A/C and Lamin B1, and changes in the …
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Fibronectin domain engineering
… a small, stable, single-domain, cysteine-free protein scaffold upon which molecular recognition capability can be engineered. In the current work, we provide substantial improvements in each phase of protein engineering through directed evolution and develop a complete platform for engineering …
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Structural and Functional Studies of the Munc13 MUN Domain and the RIM C2B Domain
… through exocytosis of synaptic vesicles. Many proteins are involved the regulation of neurotransmission. The central fusion machinery includes the SNARE proteins and Munc18- 1. Besides these universal components, many other neuronal specific proteins are also involved in regulating …
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