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- Mass Spectrometry (12)
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Articles 1 - 30 of 43
Full-Text Articles in Physical Sciences and Mathematics
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 …
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov
Doctoral Dissertations
Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Intracellular Delivery Of Therapeutic Biomolecules Through Versatile Polymer Nanotechnology, David C. Luther
Doctoral Dissertations
Advancing pharmaceutical technology has made it possible to treat diseases once considered ‘undruggable.’ Access to these new pharmaceutical targets is possible thanks to the advent of protein and nucleic acid therapeutics. Responses to the COVID-19 pandemic, as well as cutting-edge treatments for cancer and multiple sclerosis have centered on these biologic therapies, promising even greater value in the future. However, their utility is limited at a cellular level by inability to cross the plasma membrane. Nanocarrier technologies encapsulate therapeutics and facilitate uptake into the cell but are often trapped and degraded in endosomes. Arginine-functionalized gold nanoparticles (Arg-NPs) provide efficient, direct …
Chromatographic Dynamic Chemisorption, Shreya Thakkar
Chromatographic Dynamic Chemisorption, Shreya Thakkar
Masters Theses
Reaction rates of catalytic cycles over supported metal catalysts are normalized by the exposed metal atoms on the catalyst surface, reported as site time yields which provide a rigorous standard to compare distinct metal surfaces. Defined as the fraction of exposed metal surface atoms to the total number of metal atoms, it is important to measure the dispersion of supported metal catalysts to report standardized rates for kinetic investigations. Multiple characterization techniques such as electron microscopy, spectroscopy and chemisorption are exploited for catalyst dispersion measurements. While effective, electron microscopy and spectroscopy are not readily accessible due to cost and maintenance …
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 …
Manipulating The Properties Of Light-Responsive Active Lipid Bilayer Membranes: Measuring Mechanics And Probing Mechanisms, Arash Manafirad
Manipulating The Properties Of Light-Responsive Active Lipid Bilayer Membranes: Measuring Mechanics And Probing Mechanisms, Arash Manafirad
Doctoral Dissertations
This thesis explores an experimental system probing the effect of energy input (in light-responsive bilayers) on membrane physicomechanical properties and dynamics of response to a trigger. We were inspired by the ability of cell membranes to alter their elastic and permeability properties and shape in response to energy input, change in lipid chemistry, or bilayer composition. Our work demonstrates and sheds new light on the roles of lipid chemical character, light-responsive moieties' incorporation in the membrane, and the lipid bilayer's mechanical properties on membrane response to chemical tuning or energy input. To observe how lipid chemistry affects membrane physical properties …
Antibiotic Sensitivity Testing Of Foodborne Bacteria Using Surface-Enhanced Raman Spectroscopy, Joshua Gukowsky
Antibiotic Sensitivity Testing Of Foodborne Bacteria Using Surface-Enhanced Raman Spectroscopy, Joshua Gukowsky
Doctoral Dissertations
The spread of antibiotic resistant bacteria around the world has become a major public health issue, and it is essential that effective detection methods exist for identifying these organisms and preventing them from spreading throughout our food systems and into the environment. The goal of this research is to develop a novel analytical procedure that is capable of easily identifying antibiotic resistance in bacterial samples, and also provides more information about the biochemical characteristics of the bacteria and their responses to antibiotic exposure. Surface-enhanced Raman Spectroscopy (SERS), an analytical technique that uses light scattering to produce a spectrum based on …
Computational Approaches For The Multimodal Imaging Of Nanomaterials And Their Biochemical Effects, Laura J. Castellanos
Computational Approaches For The Multimodal Imaging Of Nanomaterials And Their Biochemical Effects, Laura J. Castellanos
Doctoral Dissertations
Nanomaterial delivery systems constitute a group of drug delivery vehicles that have been used extensively in biodelivery. The proper characterization of the therapeutic function of these nanomaterials requires analytical methods to track the presence of the cargo and its biochemical effects. In some cases, the detection of the cargo and biochemical changes are not attainable in the same experiment, and more than one technique might be needed for the proper analysis of the drug delivery system. In this case, separate analysis of adjacent tissue sections is performed by techniques that offer complementary information such as MALDI-MS and LA-ICP-MS. However, the …
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, …
Analysis Of Titanium Dioxide Nanoparticles In Foods Using Raman Spectroscopic Techniques, Janamkumar Pandya
Analysis Of Titanium Dioxide Nanoparticles In Foods Using Raman Spectroscopic Techniques, Janamkumar Pandya
Doctoral Dissertations
Titanium dioxide (TiO2) and its nanoparticles (NPs) are widely used in various applications. Recently, the presence of TiO2 NPs in food and consumer products raised safety concerns to human health and the environment. The goal of this project is to explore the capability of Raman Spectroscopy in the analysis of TiO2-NPs and apply this technique for the analysis of TiO2-NPs in food and environmental samples. Two approaches, i.e. the ligand-based and the mapping-based, were evaluated. The ligand-based approach utilized the surface enhanced Raman scattering (SERS) property of the TiO2 NPs as a substrate to enhance the signal of a surface …
Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati
Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati
Doctoral Dissertations
Using mass spectrometry (MS) to obtain information about a higher order structure of protein requires that a protein’s structural properties are encoded into the mass of that protein. Covalent labeling (CL) with reagents that can irreversibly modify solvent accessible amino acid side chains is an effective way to encode structural information into the mass of a protein, as this information can be read-out in a straightforward manner using standard MS-based proteomics techniques. The differential reactivity of proteins under two or more conditions can be used to distinguish protein topologies, conformations, and/or binding sites. CL-MS methods have been effectively used for …
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 …
Protein Detection And Structural Characterization By Mass Spectrometry Using Supramolecular Assemblies And Small Molecules, Bo Zhao
Doctoral Dissertations
Mass spectrometry (MS) has played an increasingly prominent role in proteomics and structure biology because it shows superior capabilities in identification, quantification and structural characterization of proteins. To realize its full potential in protein analysis, significant progress has been made in developing innovative techniques and reagents that can couple to MS detection. This dissertation demonstrates the use of polymeric supramolecular assemblies for enhanced protein detection in complex biological mixtures by MS. An amphiphilic random co-polymer scaffold is developed to form functional supramolecular assemblies for protein/ peptide enrichment. The influences of charge density and functional group pKa on host-guest interactions …
Enhanced Mass Spectrometric Analysis Of Peptides And Proteins Using Polymeric Reverse Micelles, Mahalia Adelina Corazon Paningbatan Serrano
Enhanced Mass Spectrometric Analysis Of Peptides And Proteins Using Polymeric Reverse Micelles, Mahalia Adelina Corazon Paningbatan Serrano
Doctoral Dissertations
Mass spectrometry (MS) has become a key and indispensable tool in the identification, characterization, and quantitative analysis of proteins owing to its universality, sensitivity, specificity, and its capability for multiplexed detection. Because biological samples containing these protein analytes are almost always complex systems, various techniques are employed in conjunction with MS to fully harness its analytical potential and enhance its detection capabilities. This dissertation explores the use of amphiphilic polymeric reverse micelles in enriching proteins and peptides from complex biological mixtures and in enhancing their mass spectrometric analysis. Fundamental studies that elucidate the molecular basis for the observed MS signal …
Precipitation And Coacervation In Polyelectrolyte-Colloid Systems, Fatih Comert
Precipitation And Coacervation In Polyelectrolyte-Colloid Systems, Fatih Comert
Doctoral Dissertations
Complex coacervation between oppositely charged polyelectrolytes (PEs) and colloids (i.e. micelles and proteins) has increasingly become popular due to the use of these materials in a range of applications including but not limited to personal care, biomaterials, protein purification, and food science. In taking advantage of complex coacervation, which is a liquid-liquid phase separation, precipitation has always represented a problem by introducing inhomogeneities, irreversibility and irreproducible kinetics. Therefore, understanding the dominant factors driving the formation of precipitates is important to control outcomes. In this work, we have performed comparative studies of coacervation and precipitation in model PE-colloid systems to investigate …
Novel Mass Spectrometry Methods For The Analysis Of Covalent And Non-Covalent Protein Structures And Their Influence On The Functions Of Therapeutic Proteins, Jake Pawlowski
Doctoral Dissertations
Biotherapeutics consist of biopolymers (proteins, polysaccharides, DNA, and RNA) that are used to treat a wide range of conditions from cancer to autoimmune disease to enzyme replacement. In recent years biotherapeutics have experience tremendous growth due to advances in technology and our understanding of human biology. They are very important to modern medicine due to their ability to treat diseases which are unable to be treated with small molecule-based drugs. Unlike small molecule drugs which are synthetically produced, biotherapeutics are expressed inside cells. Produced biotherapeutics are not made up of a single homogenous population but instead a population of highly …
Characterization Of Highly Heterogeneous Heparin-Protein Complexes Using Novel Mass Spectrometry-Based Approaches, Yunlong Zhao
Characterization Of Highly Heterogeneous Heparin-Protein Complexes Using Novel Mass Spectrometry-Based Approaches, Yunlong Zhao
Doctoral Dissertations
Heparin-like glycosaminoglycan (GAG) is a family of polysaccharide involved in variety of physiological processes. They have potentials to interact with a broad range of proteins and many of them hold crucial values in regulation of protein functions. My dissertation addresses the significance and challenges in the field of heparin-mediated studies, with a focus on the questions in biological and analytical aspects, which are largely hindered by the structural heterogeneity and function diversity of heparin. My dissertation reports the efforts I made in the past few years with respect to the development of novel analytical strategies based on a combination of …
Analytical Methods To Support Design And Optimization Of Protein Drug Conjugate: Focusing On Haptoglobin-Hemoglobin Complex As A Drug Carrier, Shengsheng Xu
Doctoral Dissertations
Acquired immunodeficiency syndrome (AIDS) remains one of the most serious public health challenges and a significant cause of mortality for certain populations. Despite the large number of antiretrovirals (mostly nucleotide and nucleoside analogs) developed in the past two decades, the inability of small molecule therapeutics to target HIV reservoirs directly creates a significant obstacle to their effective utilization. Indeed, achieving the desired therapeutic effect in the absence of the effective targeted delivery must rely on dosage escalation, which frequently causes severe toxicity. This problem may be solved by conjugation of antiretroviral agents to endogenous proteins (e.g., hemoglobin haptoglobin complex) that …
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. …
New Mass Spectrometric Methods For Studying Proteins In Solution And In The Gas Phase, Zhe Zhang
New Mass Spectrometric Methods For Studying Proteins In Solution And In The Gas Phase, Zhe Zhang
Doctoral Dissertations
This dissertation focuses on the mass spectrometric based methods for studying protein structures in solution phase and in gas phase. Protein structure is important to study because it is related to many disease mechanism and related therapies. The relationship between protein structures in solution phase and in gas phase has been investigated. Especially, the electrostatic interaction is characterized by mass spectrometry (MS). A HDX method has been developed to study protein oligomer kinetics and applied to study β-2-microglobulin (β2m) oligomerization. This dissertation firstly focuses on the relationship between protein gas phase structure and solution phase structure. We studied the structures …
Analysis Of Gold Nanoparticles And Their Use With Laser Desorption/Ionization Mass Spectrometry, Alyssa Marsico
Analysis Of Gold Nanoparticles And Their Use With Laser Desorption/Ionization Mass Spectrometry, Alyssa Marsico
Doctoral Dissertations
Gold nanoparticles (AuNPs) have many unique properties that make them attractive for use in various biological applications. Laser desorption/ionization mass spectrometry (LDI-MS) has been used to monitor AuNPs in complex biological samples but there are still many ways in which AuNPs can be used with MS. In this dissertation, the use of AuNPs to assist in analyte ionization has been investigated. Their ability to enhance signal from biomolecules based on their surface chemistry, size, aggregation and method of deposition has been studied. The first use of an inkjet printer to create surfaces from which analytes can be sampled is discussed …
Gold Nanoparticle Biodistributions And Stability In Vivo From Mass Spectrometric Imaging, Sukru Gokhan Elci
Gold Nanoparticle Biodistributions And Stability In Vivo From Mass Spectrometric Imaging, Sukru Gokhan Elci
Doctoral Dissertations
Their smaller size, inherent non-toxicity and tunable properties of gold nanoparticles (AuNPs) attract researchers for their use in biological applications such as drug delivery, imaging and therapeutics. Understanding the in vivo fate of these AuNPs are essential for their potential effects in both the environment and the body. In this dissertation, mass spectrometric imaging methods using laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) and laser desorption/ionization (LDI-MS) have been investigated to monitor the in vivo fate of AuNPs. AuNP injected mouse tissue samples can be obtained and readily imaged to track the injected AuNPs using these methods. A first-ever imaging …
Development Of Filter-Based Surface Enhanced Raman Spectroscopic Assays For Rapid Detection Of Chemical And Biological Contaminants In Water, Siyue Gao
Masters Theses
Surface enhanced Raman spectroscopy (SERS) has been widely applied for rapid and sensitive detection of various chemical and biological targets. Here, we incorporated a syringe filter system into the SERS method to detect pesticides, protein toxins and bacteria in water. For the detection of chemical and protein targets, silver nanoparticles (Ag NPs) were aggregated by sodium chloride (NaCl) to form nanoclusters that could be trapped in the pores of the filter membrane to from the SERS-active membrane. Then a coating of capture (e.g. aptamer) was integrated on the nanoparticle substrate if needed. Then samples were filtered through the membrane. After …
Novel Analytical Methods Combining Non-Denaturing Chromatography And Mass Spectrometry To Study Biopolymer Structure And Interactions, Khaja Muneeruddin
Novel Analytical Methods Combining Non-Denaturing Chromatography And Mass Spectrometry To Study Biopolymer Structure And Interactions, Khaja Muneeruddin
Doctoral Dissertations
Biotherapeutics, an emerging class of medicines containing biopolymers (e.g., proteins, peptide, and polysaccharides) have been developed for a variety of indications including cancer, autoimmune, genetic, and blood diseases. Among these biopolymers protein therapeutics have been the rapidly growing segment in the pharmaceutical industry. This trend combined with the complexity of proteins has necessitated the development of powerful and robust analytical methods to study their structure and interactions with physiological partners. Mass spectrometry (MS) has become an indispensable tool to analyze various attributes of protein drugs such as profiling of intact mass, amino acid sequencing, and post translational modifications (PTMs). In …
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 …
Studying Nanoparticle/Cell And Nanoparticle/Biosurface Interaction With Mass Spectrometry, Singyuk Hou
Studying Nanoparticle/Cell And Nanoparticle/Biosurface Interaction With Mass Spectrometry, Singyuk Hou
Masters Theses
Nanoparticles (NPs) have been used widely in various fields ranging from biomedical applications to life science due to their highly tunable properties. It is essential to understanding how NPs interact with biological systems of interest, therefore, analytical platforms to efficiently track NPs from cell to animal level are essential. In this thesis, laser desorption ionization mass spectrometry (LDI-MS) and inductively-coupled plasma mass spectrometry (ICP-MS) has been developed and applied to quantify NP/cell and NP/biological surface interactions. These two methods provide fast, label-free and quantitative analysis. New capability of LDI-MS to differentiate cell surface-bound and internalized NPs were established and ICP-MS …