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Site-Specific Glyco-Engineering Of Recombinant Thrombomodulin, Joseph M. Keil

ETD Archive

Thrombomodulin (TM), a membrane glycoprotein predominately expressed on endothelium, plays essential roles in regulating local hemostatic balance. Particularly, TM modulates the activity of thrombin from a procoagulant to an anticoagulant protease. When bound to TM, thrombin activates plasma protein C, which selectively inactivates coagulation factors Va and VIIIa. At the same time, TM-bound thrombin is unable to cleave fibrinogen or to activate platelets diminishing its procoagulant activity. recombinant TM456 is a promising anticoagulant candidate, but it has a very short half-life. TM is a proteoglycan and its O-linked glycosaminoglycan (GAG), chondroitin sulfate (CS), on the D3 domain contributes to TM’s …

Long Non-Coding Rnas In Inflammation, Macrophage Activation, And Inflammatory Human Diseases, Avisankar Chini

Chemistry & Biochemistry Dissertations - Archive

Inflammation and immune signaling is central to infection and diseases. Growing evidence suggests that along with protein coding genes, long non-coding RNAs (lncRNAs) play a critical role in disease onset, combat, and recovery against pathogen, damaged and self-altered cells. Our lab has been extensively studying the role of lncRNA HOTAIR (HOX transcript antisense intergenic RNA) in gene regulation and epigenetics, and eventually discovered its hidden function regulating inflammation and immune signaling in macrophage, a major type of cell involved in immunity. Previous scholars in our lab have successfully demonstrated lncRNA HOTAIR’s regulatory molecular mechanism elucidating its specific role in cellular …

Development And Applications Of Novel And Practical Fluorination Reagents., Yuhao Yang

Electronic Theses and Dissertations

The fluorine (F) atom has distinctive properties such as the highest electronegativity, small size, low polarizability, and strong C–F bond strength. Not surprisingly, fluorinated organic compounds have garnered significant attention in the pharmaceutical, agrochemical, and material fields. Since organofluorides are very rare in nature, we need fluorination reagents to help us transfer fluorine into the organic molecules. In past decades, a vast number of fluorination reagents have been developed and many of them are commercially available now. However, there is still much room for the improvement of these reagents. Our target is to develop novel and practical fluorination reagents to …

Identification Of Acidic Residues In Proteins By Selective Chemical Labeling And Tandem Mass Spectrometry, Fnu Ashima

Chemistry & Biochemistry Theses - Archive

Proteins play important role in carrying out a wide range of cellular activities. They are subjected to various post-translational modifications (PTMs) by the addition of functional groups such as acetyl, phosphoryl, and methyl which leads to changes in their biological functions, localization, activity, and structure. The growth of MS technology has immensely facilitated the identification of PTMs comprehensively. This dissertation focuses on mapping these changes using covalent labeling techniques by tagging carboxylic acid residues, which undergo various kinds of PTMs. The second chapter focuses on the methods designed for Affinity Purification Mass Spectrometry (AP-MS) chemical cross-linking (CXL) of protein complexes. …

Functional Nanocomposite Coatings For Use In Food Packaging, Camden N. Webb

Master's Theses

Plastics are a class of materials known for their cost and property advantages, increasing significantly in their usage worldwide. Unfortunately, these benefits come with an increasingly concerning environmental impact. A combination of inadequate disposal options and combinations of materials have led to environmental disasters that will impact generations. One of the worst areas for plastic waste is food packaging. Plastic as a material generally excels at durability and longevity, but as food packaging, it outlives its intended purpose by several orders of magnitude. This leads to plastic food packaging materials sitting in landfill or leading to the environment for hundreds …

Mapping Roles Of Active Site Residues In The Acceptor Site Of The Pa3944 Gcn5-Related N-Acetyltransferase Enzyme, Cillian Variot, Daniel Capule, Xhulio Arolli, Jackson Baumgartner, Cory T. Reidl, Charles Houseman, Miguel Ballicora, Daniel P. Becker Ph.D., Misty L. Kuhn

Chemistry: Faculty Publications and Other Works

An increased understanding of how the acceptor site in Gcn5-related N-acetyltransferase (GNAT) enzymes recognizes various substrates provides important clues for GNAT functional annotation and their use as chemical tools. In this study, we explored how the PA3944 enzyme from Pseudomonas aeruginosa recognizes three different acceptor substrates, including aspartame, NANMO, and polymyxin B, and identified acceptor residues that are critical for substrate specificity. To achieve this, we performed a series of molecular docking simulations and tested methods to identify acceptor substrate binding modes that are catalytically relevant. We found that traditional selection of best docking poses by lowest S scores …

Investigating The Effects Of E219 Mutations In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase, Cinthya Moran

Theses, Dissertations and Culminating Projects

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis. Tuberculosis drug resistance is increasingly a problem, but recent research has provided results that suggest Indole-3-Glycerol Phosphate Synthase (IGPS) could be a potential drug target. IGPS is an enzyme that catalyzes the fourth step in the tryptophan biosynthesis pathway, a crucial process for optimal Mycobacterium tuberculosis growth. In this research, we studied IGPS from Mycobacterium tuberculosis (MtIGPS) to shed light on a particular conserved residue that has not been studied in depth in any IGPS homolog. My investigation focuses on understanding the role of the active site residue E219. …

Exploiting Natural Rna 2′-5′-Linkage In Nucleic Acid Aptamers And Dna Nanostructures, Johnsi Mathivanan

Legacy Theses & Dissertations (2009 - 2024)

Developments in chemical synthesis of nucleic acid sequences and modifications have aided in the study of biomolecular interactions and the roles of modified nucleic acids in biology, medicine, and nanotechnology. This work describes some of the aspects of such developments, from synthesis of chemically modified RNA and DNA aptamers that can bind antibiotics and metal ions to the use of nucleic acids with novel backbone linkages in the construction of nanostructures. Analysis of such nucleic acid structures inform us on the basic structure of these molecules and the resulting functions that are applicable in fields such as biosensing, drug screening …

Distinguishing Between Living And Dead Plant Material From The Red Spruce Using Atr Ft-Ir Spectroscopy, Bailey Ann Hoplight

Legacy Theses & Dissertations (2009 - 2024)

Spectroscopic methods have recently been used to analyze plant species and maturation. However, there is a lack of research into employing spectroscopy for distinguishing living plant material and dead plant material, which is important for the agriculture and environmental health fields. Here in this study, we have shown the potential of ATR-FT IR (Attenuated total reflectance Fourier transformed infrared spectroscopy) to classify plant materials as living or dead through the help of multivariate statistical analysis methods. Plant samples were from the roots and needles of picea rubens, more commonly known as the red spruce tree. The samples were classified by …

Studying The Stability Of Collagen/Heparin Coatings To Be Used In Cell Therapy Applications, Gavin Mussino

Biological Sciences Undergraduate Honors Theses

This honors thesis aims to investigate the reusability and performance of cell coatings for cell therapy applications. Cell therapy, which involves the use of human cells to repair or replace damaged tissues, holds immense potential for medical advancements. However, ensuring the survival and functionality of transplanted cells remains a significant challenge. We focused on studying the effectiveness of coatings applied to cells for improved cell growth and viability. The research project involved the preparation of the coatings using a layer-by-layer method and the subsequent seeding of cells. The coated cells were then subjected to a series of experiments to assess …

Probing The Mechanism Of Dna Protein Crosslink Formation By Aziridinomitosenes Through The Selective Precipitation Of Protein Salts, Michael Blair

Boise State University Theses and Dissertations

Aziridinomitosenes are synthetic chemotherapeutic agents that are analogs of Mitomycin C, as well as other mitomycins. They are known for their ability to form DNA interstrand cross-links (ICLs), and more recently have been observed to form DNA-protein cross-links (DPCs). In this work, three synthetic aziridinomitsenes were prepared and studied to better understand the role of the C6 and C7 positions in the formation of DNA-protein cross-links. In addition, two separate methods, the advanced recovery of K-SDS precipitates and the K-SDS assays were utilized and compared to assess the advancements in the analysis of DPC formation. H AZM, C6 AZM, Dimethyl …

Phase Distribution Of Nickel, Chromium, And Cobalt In Seawater At Olivine-Enriched Beaches: Implications For Carbon Capture By Enhanced Silicate Weathering, Nathaniel J. Padrnos

Master's Theses

The application of olivine to coastal areas is a proposed method of removing carbon dioxide from the atmosphere for climate change mitigation. Olivine is abundant and dissolves relatively fast, but it contains trace amounts of nickel (Ni), chromium (Cr), and cobalt (Co) which may be toxic to marine biota in cases of widespread coastal olivine spreading. Prior studies have suggested that Ni concentrations in marine sediments and/or the overlying water column due to olivine dissolution could be a limiting factor for its carbon capture potential. Therefore, it is critical to understand and model the processes affecting trace metal bioavailability after …

Electron-Transfer Mediated Photo-Switching In Nanoparticles, Liaoran Cao

All Dissertations

Previous publications from our lab demonstrated viable approaches to design a photo-switching nanoparticle with arguably superior brightness and photostability resulting in an improved resolution in localization-based microscopy, as compared to other photo-switching dyes or particles. As a follow-up, this dissertation is focused on two major tasks: first, developing nanoparticles with better photo-switching properties for super-resolution imaging; second, trying to achieve a better physical picture of the mechanisms involved in photo-switching, including polaron dynamics, charge transfer, and energy transfer. A new class of photo-switchable nanoparticles was developed by blending conjugated polymer semiconductor with fullerene-based electron acceptors, and further blending with polystyrene …

Synthesis And Reactivity Of Heteroatom Embedded Cycloalkynes In Spaac, Nickel Catalyzed Alkylarylation Of Alkenes, And Carbofluorination Of Alkynes, Namrata Khanal

Chemistry and Chemical Biology ETDs

Part I covers Chapters 1, 2, and 3

cycloaddition reactions, that is utilized in biorthogonal chemistry. This metal free version The strain promoted azide-alkyne cycloaddition (SPAAC) reaction is one of the popular 1,3-dipolar of click reaction offers advantage over copper catalyzed click reaction. Since it eliminates the use of copper that is toxic to cells, it is considered favorable for biocompatible reaction. Due to the increased reactivity with dipoles without the use of metal catalyst, cycloalkynes, in particular cyclooctynes, have been employed as the biorthogonal reagent in biorthogonal chemical reaction for the study of a biological processes in vivo. The …

Integrating Sensor Development, Risk Assessment, And Community Engagement To Support Environmental Justice In The Rural Community Of El Tiple, Colombia, David Bahamon Pinzon

All Dissertations

In Colombia, ethnic communities have traditionally been responsible stewards of natural resources. They recognize the importance of these resources for their livelihood, as well as their ancestral and cultural heritage. El Tiple, a rural Afro-Colombian community, has been affected by the incursion of private corporations that promoted the expansion of sugarcane monocrops in their territory. Since the introduction of the monoculture industry, local freshwater sources have been depleted due to intensive water use for irrigation of the sugarcane crops. Additionally, the intensive usage of agrochemicals has been linked with loss of native flora, damages to family farms, and pollution of …

Removal Of Nonylphenols From Water And Wastewater Using Alginate-Activated Carbon Beads, Angelica Araly Chacon

Open Access Theses & Dissertations

The presence of contaminants of emerging concern (CECs) have been affecting water quality in recent years. The United States Environmental Protection Agency (U.S EPA) defines CECs as toxic chemicals without regulatory status and with adversely impact on the wildlife and people. Among the CECs, nonylphenols (NPs) are frequently found in all water systems and are categorized as endocrine-disrupting compounds (EDCs) due to their ability to mimic hormones causing reproductive and developmental effects in humans and animals. The main sources of discharge and distribution of NPs into the environment are wastewater treatment plants (WWTPs) which are not designed to remove them. …

Manufacturing Of A Flexible Piezoelectric Nanogenerator By Functionalizing Polyvinylidene Fluoride With Lithium Tantalate And Multiwalled Carbon Nanotubes For Energy Harvesting And Sensing Applications, Islam Uddin Shipu

Theses and Dissertations

Mechanical energy is one of the readily accessible green energy sources that could be employed to meet the small-scale energy requirement. In order to capture mechanical energy, power the next generation of electronic gadgets, and health monitoring flexible piezoelectric nanogenerators made of light weight polymers and carbon nanotubes have drawn a lot of attention. Lithium tantalate (LiTaO3), a ferroelectric substance, was prepared here and utilized to create a flexible piezoelectric nanogenerator (FPNG). A compact piezoelectric nanogenerator that successfully transfers mechanical energy into electricity was then created using lightweight polyvinylidene fluoride (PVDF), multi-walled carbon nanotube (MWCNT), and LiTaO3 nanoparticles. To create …

Phosphatase And Pseudo-Phosphatase Functions Of Phosphatase Of Regenerating Liver 3 (Prl-3) Are Insensitive To Divalent Metals In Vitro, Jeffery T. Jolly, Ty C. Cheatham, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Phosphatase of regenerating liver 3 (PRL-3) is associated with cancer metastasis and has been shown to interact with the cyclin and CBS domain divalent metal cation transport mediator (CNNM) family of proteins to regulate the intracellular concentration of magnesium and other divalent metals. Despite PRL-3’s importance in cancer, factors that regulate PRL-3’s phosphatase activity and its interactions with CNNM proteins remain unknown. Here, we show that divalent metal ions, including magnesium, calcium, and manganese, have no impact on PRL-3’s structure, stability, phosphatase activity, or CNNM binding capacity, indicating that PRL-3 does not act as a metal sensor, despite its interaction …

Structures Of The Insecticidal Toxin Complex Subunit Xpta2 Highlight Roles For Flexible Domains, Cole L. Martin, David W. Chester, Christopher D. Radka, Lurong Pan, Zhengrong Yang, Rachel C. Hart, Elad M. Binshtein, Zhao Wang, Lisa Nagy, Lawrence J. Delucas, Stephen G. Aller

Markey Cancer Center Faculty Publications

The Toxin Complex (Tc) superfamily consists of toxin translocases that contribute to the targeting, delivery, and cytotoxicity of certain pathogenic Gram-negative bacteria. Membrane receptor targeting is driven by the A-subunit (TcA), which comprises IgG-like receptor binding domains (RBDs) at the surface. To better understand XptA2, an insect specific TcA secreted by the symbiont X. nematophilus from the intestine of entomopathogenic nematodes, we determined structures by X-ray crystallography and cryo-EM. Contrary to a previous report, XptA2 is pentameric. RBD-B exhibits an indentation from crystal packing that indicates loose association with the shell and a hotspot for possible receptor binding or a …

Extraction, Purification, And Characterization Of Potential Bioactive Compounds Produced By Janthinobacterium Lividum Tajx1901, Andy Elorm Agbakpo

Electronic Theses and Dissertations

Underexplored environments such as soil samples continue to be an untapped source of bacterial strains with great potential to produce secondary metabolites for medicinal applications. As a result, these microorganisms represent a broad and yet unknown reservoir of new strains capable of producing these novel compounds. The current research primarily seeks to perform the isolation, purification, and characterization of secondary metabolites from a soil bacterium (Janthinobacterium lividum TAJX1901). The isolated soil bacterium was successfully cultured on rich media agar plates, followed by extraction using methanol and chloroform. The purification methods utilized include flash column chromatography, preparative thin-layer chromatography, and …

Isolation And Structural Determination Of Bioactive Metabolites From The Soil Bacterium, Arthrobacter Sp. Tajx1902, Amonah Arije

Electronic Theses and Dissertations

As antimicrobial resistance persistently disrupts the treatment of microbial infection, natural product chemistry has played a significant role in identifying novel drugs with novel modes of action critical to getting ahead of resistance. The primary goal of this project is to extract and identify potential novel antimicrobial natural products produced by Arthrobacter sp. Although underexplored, Arthrobacter sps. have been known to produce bioactive compounds with versatility; one such is a depsipeptide with quorum-sensing inhibitory activity.¹ In this research, an Arthrobacter sp. TAJX1902, isolated from a soil sample, showed inhibitory activity against a filamentous indicator bacterium and a violacein-producing Janthinobacterium …

Characterization Of Mechanically Recycled Polylactic Acid (Pla) Filament For 3d-Printing By Evaluating Mechanical, Thermal, And Chemical Properties And Process Performance, Mahsa Shabani Samghabady

All Theses

Polylactic acid (PLA) is a biopolymer made from renewable resources such as sugar and corn. PLA filament is a popular material used in Fused Deposition Modeling (FDM) 3D-printing. While this material has many advantages, all the failed parts, support structures, rafts, nozzle tests, and the many prototype iterations during the 3D-printing process contribute to the plastic pollution and release of greenhouse gases. Although PLA is biodegradable, it can take years to degrade in landfills. Instead of throwing away PLA waste and buying new filaments, PLA can be recycled. Amongst the different recycling technologies, mechanical recycling is the most environmentally friendly. …

Differential Membrane Binding Of Α/Β-Peptide Foldamers: Implications For Cellular Delivery And Mitochondrial Targeting, Tzong-Hsien Lee, James W. Checco, Tess Malcolm, Chelcie H. Eller, Ronald T. Raines, Samuel H. Gellman, Erinna F. Lee, W. Douglas Fairlie, Marie-Isabel Aguilar

Department of Chemistry: Faculty Publications

The intrinsic pathway of apoptosis is regulated by the Bcl-2 family of proteins. Inhibition of the anti-apoptotic members represents a strategy to induce apoptotic cell death in cancer cells. We have measured the membrane binding properties of a series of peptides, including modified α/β-peptides, designed to exhibit enhanced membrane permeability to allow cell entry and improved access for engagement of Bcl-2 family members. The peptide cargo is based on the pro-apoptotic protein Bim, which interacts with all anti-apoptotic proteins to initiate apoptosis. The α/β-peptides contained cyclic β-amino acid residues designed to increase their stability and membrane-permeability. Dual polarisation interferometry was …

Organocatalyzed Four-Component On-Water Green Synthesis Of Spiroindolinpyranopyrazole, Tanzida Zubair

Theses and Dissertations

Although many synthetic and natural pharmaceuticals and drug-like compounds contain spiro center(s) in their structures, the synthesis of spiro centers is seen to be an exciting and difficult area of research. The synthesis of spiro compounds and their derivatives was carried out using a four-component process that included reagents like hydrazine hydrate, isatin, malononitrile, and an active methylene compound like ethyl acetoacetate. Microwave irradiation was used in a short time range (5 – 30 min) and moderate temperature (80°C), with water as a solvent, and N, N-Diisopropylethylamine (DIPEA) as a catalyst to give high yield of products. Our process complies …

Next-Generation Nanopore Sensors Based On Conductive Pulse Sensing For Enhanced Detection Of Nanoparticles, Samuel Confederat, Seungheon Lee, Derr Vang, Dimitrios Soulias, Fabio Marcuccio, Timotheus I. Peace, Martin Andrew Edwards, Pietro Strobbia, Devleena Samanta, Christoph Wälti, Paolo Actis

Chemistry & Biochemistry Faculty Publications and Presentations

Nanopore sensing has been successfully used to characterize biological molecules with single-molecule resolution based on the resistive pulse sensing approach. However, its use in nanoparticle characterization has been constrained by the need to tailor the nanopore aperture size to the size of the analyte, precluding the analysis of heterogeneous samples. Additionally, nanopore sensors often require the use of high salt concentrations to improve the signal-to-noise ratio, which further limits their ability to study a wide range of nanoparticles that are unstable at high ionic strength. Here, a new paradigm in nanopore research that takes advantage of a polymer electrolyte system …

Aerosol Mutagenicity In San Bernardino, California Via Bacterial Fluctuation Tests, Sean Murphy

Electronic Theses, Projects, and Dissertations

San Bernardino, California’s poor air quality is a health risk to its population with some of the highest concentrations of ozone and aerosol in the United States. Aerosols are solid or liquid particles suspended in the air. Smaller aerosol particles are the most harmful as they are more likely to penetrate further into the respiratory system. These aerosols can cause respiratory issues and contain toxic compounds. One measure of aerosol toxicity is to study the mutagenicity of the aerosol. To study the mutagenicity of aerosol samples collected in San Bernardino in 2022, fluctuation tests (based on the Ames test for …

Expansion Of The Diazacyclobutene Motif For Antiparasitic Evaluation, Brock Alexander Miller

All Dissertations

Molecules containing N-heterocycles are prevalent in pharmaceutical settings. The ability to generate highly functionalized molecules containing N-heterocycles in very few synthetic operations is valuable for drug discovery. Our group has developed a two-step synthesis to access a rarely studied diazacyclobutene scaffold via a formal [2+2] cycloaddition between 4-phenyl-1,2,4-triazolinedione and electron-rich thioalkynes. Our interest in this scaffold increased exponentially from promising preliminary biological evaluations against a protozoan parasite, Trypanosoma brucei. While we were able to double the number of historical examples of this scaffold, there were significant limitations in our methodology. The most notable limitations were the lack …

Atom Economical Reactions Of Terpenoids And Post-Consumer Plastics With Sulfur, Charini Maladeniya

All Dissertations

The production of Ordinary Portland Cement (OPC) and its uses have a complicated environmental impact, which is influenced by infrastructure development and building operations as well as CO₂ emissions, which account for 7% of all worldwide CO₂ emissions. Due to the increasing population, production is still ongoing. The search for cement and construction materials produced with zero to low CO₂ emissions is therefore continuous. Finding recyclable, CO₂ gas-free biocomposites with high sulfur content that can rival the mechanical properties of popular building supplies like Portland cement is the primary objective of the research discussed in this …

The Influence Of Allostery Governing The Changes In Protein Dynamics Upon Substitution, Joseph Hess

All Dissertations

The focus of this research is to investigate the effects of allostery on the function/activity of an enzyme, human immunodeficiency virus type 1 (HIV-1) protease, using well-defined statistical analyses of the dynamic changes of the protein and variants with unique single point substitutions ¹. The experimental data¹ evaluated here only characterized HIV-1 protease with one of its potential target substrates. Probing the dynamic interactions of the residues of an enzyme and its variants can offer insight of the developmental importance for allosteric signaling and their connection to a protein’s function. The realignment of the secondary structure elements can …

Synthesis And Characterization Of Cobalt(Iii) Complexes And A Vanadium(Iv) Complex With Flavonoids As Ligands, Ethan Schroeder

Chemistry & Biochemistry Theses & Dissertations

For many years now, transition metal complexes have been used as favorable additional chemotherapeutic approaches to medicine that were previously unexplored in the literature. One well-known chemotherapeutic drug, cisplatin, has been applied, but is limited in use due to its toxicity to the cells and its undesirable side effects to humans. Newly developed cobalt-based complexes with ligands known as flavonoids are being used to fight cancer. Flavonoids, compounds mainly found in fruits and vegetables, are shown to have antioxidative and anticancer properties. Use of flavonoids as ligands in transition metal complexes, e.g., those with a Ru(II) metal center, have been …