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Articles 1 - 21 of 21
Full-Text Articles in Biochemistry
High Resolution Mass Spectrometry As A Platform For The Analysis Of Polyoxometalates, Their Solution Phase Dynamics, And Their Biological Interactions., Daniel T. Favre
High Resolution Mass Spectrometry As A Platform For The Analysis Of Polyoxometalates, Their Solution Phase Dynamics, And Their Biological Interactions., Daniel T. Favre
Doctoral Dissertations
Polyoxometalates (POMs) are a class of inorganic molecule of increasing interest to the inorganic, bioinorganic and catalytic communities among many others. While their prevalence in research has increased, tools and methodologies for the analysis of their fundamental characteristics still need further development. Decavanadate (V10) specifically has been postulated to have several unique properties that have not been confirmed independently. Mass spectrometry (MS) and its ability to determine the composition of solution phase species by both mass and charge is uniquely well suited to the analysis of POMs. In this work we utilized high-resolution mass spectrometry to characterize V10 in aqueous …
Deciphering Protein Higher-Order Structure And Interactions Via Diethylpyrocarbonate Labeling-Mass Spectrometry, Xiao Pan
Doctoral Dissertations
The study of protein higher-order structures is vital because it is closely related to the investigation of protein folding, aggregation, interaction and protein therapeutics. Consequently, numerous biochemical and biophysical tools have been developed to study protein higher-order structures in many different situations. The combination of covalent labeling (CL) and mass spectrometry (MS) has emerged as a powerful tool for studying protein structures and offers many advantages over other traditional techniques, such as better structural coverage, high throughput, high sensitivity, and the ability to study proteins in mixtures. This dissertation focuses on diethylpyrocarbonate (DEPC) as an effective CL reagent that can …
Quantitative Imaging Of Tensile Forces At Cell-Cell Junction With Dna-Based Probes, Puspam Keshri
Quantitative Imaging Of Tensile Forces At Cell-Cell Junction With Dna-Based Probes, Puspam Keshri
Doctoral Dissertations
Mechanical forces are an integral part in biology, they regulate several cellular properties, such as morphology, proliferation, migration. These forces are also involved in receptor signaling and the differentiation of different cell types. Different proteins and biomolecules such as cadherin, integrin, notch proteins are essential elements of these processes. Measuring these intercellular forces are challenging considering the minimal intensity (piconewton-level) of these molecular forces. In our lab, we have developed a membrane DNA tension probe (MDTP) that uses a DNA hairpin module to sense tensile forces and has a lipid anchor to modify onto live-cell membranes. The programmability of DNA …
Amyloidogenesis Of Β-2-Microglobulin Studied By Mass Spectrometry And Covalent Labeling, Blaise G. Arden
Amyloidogenesis Of Β-2-Microglobulin Studied By Mass Spectrometry And Covalent Labeling, Blaise G. Arden
Doctoral Dissertations
Amyloid-forming proteins are implicated in a number of debilitating diseases. While many amyloid-forming proteins are well studied, the early stages of amyloidosis are still not well understood on a molecular level. Covalent labeling, combined with mass spectrometry (CL-MS), is uniquely well suited to provide molecular-level insight into the factors governing the early stages of amyloidosis. This dissertation leverages CL-MS techniques to examine the early stages of β-2-microglobulin (β2m) amyloidosis. β2m is the protein that forms amyloids in the condition known as dialysis-related amyloidosis. An automated CL-MS technique that uses dimethyl(2-hydroxy-5-nitrobenzyl) sulfonium bromide as a labeling reagent was developed and used …
Investigating The Accumulation, Sub-Organ Distribution, And Biochemical Effects Of Nanomaterials Using Mass Spectrometry, Kristen Nicole Sikora
Investigating The Accumulation, Sub-Organ Distribution, And Biochemical Effects Of Nanomaterials Using Mass Spectrometry, Kristen Nicole Sikora
Doctoral Dissertations
Gold nanoparticles (AuNPs) are attractive materials for use in various biomedical applications, such as therapeutic delivery, due to their unique chemical properties and modular tunability. Mass spectrometry methods, including laser desorption/ionization mass spectrometry (LDI-MS) and inductively coupled plasma mass spectrometry (ICP-MS) have been successfully used to evaluate the distribution of AuNPs in complex biological systems. As new AuNP-based materials are developed for applications in therapeutic delivery, it is essential to simultaneously develop analytical techniques that can comprehensively assess their behavior in vivo. In this dissertation, novel mass spectrometric methods have been developed and utilized to evaluate the uptake, distribution, …
Study Of The Role Of Biologically-Relevant, Labile Nickel Pools In The Maturation Of Nickel-Dependent Enzymes, Priyanka Basak
Study Of The Role Of Biologically-Relevant, Labile Nickel Pools In The Maturation Of Nickel-Dependent Enzymes, Priyanka Basak
Doctoral Dissertations
Cellular nickel pools, comprised of static and labile pools of nickel complexes, play important roles in maintaining nickel homeostasis in various organisms (microbes, fungi, and plants), which utilize it as a cofactor of one or more nickel enzymes that catalyze specific reactions and are essential for their proper growth and survival in various ecological niches. Like other metals, tight regulation of cellular nickel levels is critical to prevent toxic effects of nickel deprivation, nickel overload, and ‘free’ nickel. While more static nickel pools include nickel tightly bound to nickel-dependent enzymes, nickel in the labile pool is exchangeable and weakly bound …
Characterization Of Biodistribution Of Transferrin And Receptor Binding Mechanism By Mass Spectrometry, Hanwei Zhao
Characterization Of Biodistribution Of Transferrin And Receptor Binding Mechanism By Mass Spectrometry, Hanwei Zhao
Doctoral Dissertations
Protein-based therapeutics have emerged as a key driver of rapid growth in drug development pipelines. However, developing such protein drugs is not straightforward in most cases, the existence of physiological barriers greatly restricts the efficient delivery of many therapeutic molecules, and therefore limits their clinical applications. A promising way to address this challenge takes advantage of certain transport protein which can effectively across and enhance the permeability of these barriers, such as transferrin (Tf) which can be internalized by malignant cells and cross physiological barriers via transferrin receptor (TfR)-mediated endocytosis and transcytosis. However, developing such products is impossible without successfully …
Covalent Labeling-Mass Spectrometry For Characterizing Protein-Ligand Complexes, Tianying Liu
Covalent Labeling-Mass Spectrometry For Characterizing Protein-Ligand Complexes, Tianying Liu
Doctoral Dissertations
This dissertation focuses on applying covalent labeling (CL) and mass spectrometry (MS) for characterizing protein-ligand complexes. Understanding protein-ligand interactions has both fundamental and applied significance. Covalent labeling is a protein surface modification technique that selectively modifies solvent-exposed amino acid side chains of proteins. A covalent bond is formed between the functional groups of labeling reagent and protein’s side chain. One of the key factors that affects CL reactivity is a side chain’s solvent accessibility. Ligand binding protects residues on the protein surface from being labeled, and residues involved in ligand binding can be indicated via decreases in labeling extents. The …
Characterization Of Β-2-Microglobulin Pre-Amyloid Oligomers And Their Role In Amyloid Inhibition, Tyler M. Marcinko
Characterization Of Β-2-Microglobulin Pre-Amyloid Oligomers And Their Role In Amyloid Inhibition, Tyler M. Marcinko
Doctoral Dissertations
In dialysis patients, β-2 microglobulin (β2m) can aggregate and eventually form amyloid fibrils in a condition known as dialysis-related amyloidosis, which deleteriously affects joint, bone, and organ function, and eventually causes organ failure. To understand the early stages of the amyloid assembly process, we have employed a series of biophysical tools including chromatography, spectroscopy, and most especially, native electrospray ionization (ESI) together with ion mobility mass spectrometry (IM-MS) to study soluble pre-amyloid oligomeric species. We have also collaborated and integrated computational modeling to help better understand and rationalize the structural basis behind oligomerization. Recently, several small molecules have been identified …
Bio-Inspired Polymers That Bind And Deliver Protein Cargo, Nicholas D. Posey
Bio-Inspired Polymers That Bind And Deliver Protein Cargo, Nicholas D. Posey
Doctoral Dissertations
Delivering functional proteins and antibodies into cells can allow researchers to probe the intracellular environment, discover new cellular pathways, and pioneer new therapeutics. However, the entry of exogenous, charged molecules, like proteins, into the cell is usually restricted by the membrane, thereby hindering intracellular delivery. Membrane permeable molecules such as cell penetrating peptides (CPPs) and protein transduction domains (PTDs) can be used to bypass the cell membrane and deliver protein into the cell, but these peptides involve iterative and laborious syntheses and are limited in terms of their chemical diversity. This dissertation work overall focuses on the design and synthesis …
Relationship Between Structure And Function In Nickel Proteins And Enzymes, Carolyn Carr
Relationship Between Structure And Function In Nickel Proteins And Enzymes, Carolyn Carr
Doctoral Dissertations
Nickel is a rarely used but biologically important metal that is utilized in all three domains of life. In nickel utilizing organisms there is a corresponding trafficking system specifically designed to capture nickel, deliver, and export excess nickel to prevent toxic effects. It is critical to understand the mechanisms by which organisms achieve metal selectivity to duplicate or disrupt this process for the benefit of human health and to further understanding of regulation mechanisms in biology. RcnR is a Ni(II) and Co(II) responsive transcriptional regulator in E. coli. The research reported in this dissertation focuses on the relationship between …
Mechanistic Studies Of Proton Gradient-Driven Protein Translocation By Droplet-Interface Bilayer Techniques, En-Hsin Lee
Mechanistic Studies Of Proton Gradient-Driven Protein Translocation By Droplet-Interface Bilayer Techniques, En-Hsin Lee
Doctoral Dissertations
Transmembrane proton gradient plays a fundamental role in protein translocation across cellular membranes, including the transport of secreted enzymes from bacterial pathogens into host cells. Much attention has been devoted to understanding the machinery of such delivery and how it functions. Over the past decade, translocation of anthrax toxin has been widely studied not only because of its central role in the deadly pathogenesis of Bacillus anthracis, but also because that it is one of the most tractable toxins and thus serves as an attractive model for studying the translocation machinery that is dependent on proton gradient across membrane. …
Kinetic And Dynamic Insights Into The Substrate Interactions And Catalysis Of Factor Inhibiting Hif-1 (Fih-1), Cristina B. Martin
Kinetic And Dynamic Insights Into The Substrate Interactions And Catalysis Of Factor Inhibiting Hif-1 (Fih-1), Cristina B. Martin
Doctoral Dissertations
inhibiting HIF-1 (FIH-1) modulates the master regulator of hypoxia sensing, hypoxia inducible factor-1 (HIF-1), by transcriptional repression making it an attractive potential target for treatment of hypoxia-related diseases. Given that similar enzymes are present within the cell and that they have other important physiological roles, defining the therapeutic window by which it can be selectively targeted becomes an issue. Consequently, it’s necessary to have a deeper understanding of the substrate interactions in FIH-1 that contributes to catalysis as this is one avenue that can be explored for future therapeutic investigations. The overall goal of this dissertation is to gain kinetic …
The Application Of Hydrogen/Deuterium Exchange And Covalent Labeling Coupled With Mass Spectrometry To Examine Protein Structure, Nicholas B. Borotto
The Application Of Hydrogen/Deuterium Exchange And Covalent Labeling Coupled With Mass Spectrometry To Examine Protein Structure, Nicholas B. Borotto
Doctoral Dissertations
Thorough insight into a protein’s structure is necessary to understand how it functions and what goes wrong when it malfunctions. The structure of proteins, however, is not easily analyzed. The analysis must take place under a narrow range of conditions or risk perturbing the very structure being probed. Furthermore, the wide diversity in size and chemistry possible in proteins significantly complicates this analysis. Despite this numerous methods have been developed in order to analyze protein structure. In this work, we demonstrate that mass spectrometry (MS)-based techniques are capable of characterizing the structure of particularly challenging proteins. This is done through …
Responsive Supramolecular Assemblies Based On Amphiphilic Polymers And Hybrid Materials, Longyu Li
Responsive Supramolecular Assemblies Based On Amphiphilic Polymers And Hybrid Materials, Longyu Li
Doctoral Dissertations
The design and synthesis of responsive supramolecular assemblies are of great interest due to their applications in a variety of areas such as drug delivery and sensing. We have developed a facile method to prepare self-crosslinking disulfide-based nanogels derived from an amphiphilic random copolymer containing a hydrophilic oligo-(ethylene glycol)-based side-chain functionality and a hydrophobic pyridyl disulfide functional group. This thesis first provides a concept of studying the influence of Hofmeister ions on the size and guest encapsulation stability of a polymeric nanogel. The size and core density of nanogel can be fine-tuned through the addition of both chaotropes and kosmotropes …
Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells, Amanda M. Hussey
Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells, Amanda M. Hussey
Doctoral Dissertations
Proper detection is the key to studying any processes on the cellular scale. Nowhere is this more evident than in the tight space which confines the synaptic cleft. Being able to ascertain the location of receptors on live neurons is fundamental to our understanding of not only how these receptors interact and move inside the cell but also how neurons function. Most detection methods rely on significantly altering the receptor; both tagging with a fluorescent protein or targeting the receptor by a fluorescent reporter in the form of a small molecule causes significant difficulties. These localization techniques often result in …
Inhibition And Cofactor Targeting Of Hypoxia-Sensing Proteins, Cornelius Y. Taabazuing
Inhibition And Cofactor Targeting Of Hypoxia-Sensing Proteins, Cornelius Y. Taabazuing
Doctoral Dissertations
Hypoxia Inducible Factor (HIF) is a transcription activator considered to be the main regulator of O2 homeostasis in humans. The transcriptional ability of HIF is regulated by the Fe2+/αKG-dependent enzyme, Factor Inhibiting HIF (FIH). FIH uses molecular oxygen to catalyze hydroxylation of an asparagine residue (Asn803) in the C-terminal transactivation domain (CTAD) of the HIFα subunit, abrogating HIF target gene expression. The mechanism of FIH and other αKG-dependent oxygenases involves the ordered sequential binding of αKG, substrate, and O2, which becomes activated to form a reactive ferryl intermediate that hydroxylates the substrate. The …
Nanoparticle Building Blocks For Functional Structures, Youngdo Jeong
Nanoparticle Building Blocks For Functional Structures, Youngdo Jeong
Doctoral Dissertations
A major goal in material science is achieving a desired function using structures fabricated with designed building blocks. Advanced synthetic and self-assembly techniques allow various nanomaterials to become promising building blocks, providing the control of the interaction between building blocks. The unique properties of nanomaterials can be transferred to structured systems. Among nanomaterials, inorganic nanoparticles such as gold nanoparticles (AuNPs), magnetic particles, and quantum dots (QDs) provide useful physical properties stemming from their inorganic core, large surface areas, and oriented surface functionalities. My research has focused on fabricating functional systems using gold nanoparticles (AuNPs), manipulating the interaction between AuNPs, bio-entities, …
Protein Behavior Directed By Heparin Charge And Chain Length, Burcu Baykal Minsky
Protein Behavior Directed By Heparin Charge And Chain Length, Burcu Baykal Minsky
Doctoral Dissertations
Glycosaminoglycans (GAGs), highly charged biological polyelectrolytes, are of growing importance as biomaterials and pharmaceutical drugs due to their immense range of physiological functions. They bind to many proteins; however, the degree of structural selectivity in GAG-protein interactions is largely unknown .Our studies have focused on the importance of heparin (a model GAG) charge and chain length in protein binding in order to explore its potential applications in biofunctional tissue scaffold materials, as polysaccharide drugs in anticoagulation, and as inhibitory agents in protein aggregation. We used electrospray ionization mass spectrometry, capillary electrophoresis, size exclusion chromatography, dynamic/static light scattering and electrostatic protein …
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres
Doctoral Dissertations
Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …
Engineering The Nanoparticle Surface For Protein Recognition And Applications, Mrinmoy De
Engineering The Nanoparticle Surface For Protein Recognition And Applications, Mrinmoy De
Open Access Dissertations
Proteins and nanoparticles (NPs) provide a promising platform for supramolecular interaction. We are currently exploring both fundamental and applied aspects of this interaction. On the fundamental side, we have fabricated a series of water-soluble anionic and cationic NPs to interact with cationic and anionic proteins respectively. A Varity of studies such as, activity assay, fluorescence titration, isothermal titration calorimetry etc. were carried out to quantify the binding properties of these functional NPs with those proteins. Those studies reveal the prospect of tuning the affinity between the nanoparticles and proteins by the surface modification. On the application side, we have used …