Chemistry Commons^™

Study Of Biologically Important Macromolecules By Nuclear Magnetic Resonance, Christopher Michael Demott

Legacy Theses & Dissertations (2009 - 2024)

Intrinsically disordered proteins or unstructured segments within proteins play an important role in cellular physiology and pathology. A combination of peptide aptamers selected by using the yeast-two-hybrid scheme, and in-cell NMR identified high affinity binders to a transiently structured intrinsically disordered proteins (IDP). This method was validated using the prokaryotic ubiquitin-like protein, Pup, of the Mycobacterium proteasome. We discover two peptide aptamers that bind to opposite sites of a transient helix in Pup, an intrinsically disordered protein, that have vastly different effects on the survival of Mycobacterium bovis BCG.

Investigating The Role Of Epitranscriptomics In Viral Immunity, Kaycie S. Lawson

Legacy Theses & Dissertations (2009 - 2024)

The characterization of host-virus relationships is essential for understanding the process of viral replication and driving the development of effective viral targeting strategies. In this work, I tested the hypothesis that ribonucleic acid (RNA) post-transcriptional modifications (PTMs) may play a significant role in defining host-virus interactions. The model system consisted of a yeast strain capable of harboring the endogenous L-A virus, which allowed me to evaluate the possible involvement of PTMs in the process of cellular immunity to virus-borne toxicity. A mass spectrometry-based platform was utilized to compare the global PTM profile of wild-type yeast with those of the same …

Further Development Of Raman Spectroscopy For Body Fluid Investigation : Forensic Identification, Limit Of Detection, And Donor Characterization, Claire K. Muro

Legacy Theses & Dissertations (2009 - 2024)

The challenges to forensic body fluid analysis have placed limitations on the type of information that investigators can acquire and how that information can be collected. In recent years, Raman spectroscopy has proven itself useful for characterizing body fluids. In 2008, a large-scale investigation was undertaken to explore the use of Raman spectroscopy as a means of identifying body fluids. This work resulted in multidimensional Raman spectroscopic signatures for the five main body fluids: semen, peripheral blood, saliva, vaginal fluid, and sweat. These studies were incredibly successful and created the foundation for years of continued research. Accordingly, the studies included …

Discovering Small Molecule Inhibitors Targeted To Ligand-Stimulated Rage-Diaph1 Signaling Transduction, Jinhong Pan

Legacy Theses & Dissertations (2009 - 2024)

The receptor of advanced glycation end product (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules, which plays an important role in immune responses. Full-length RAGE includes three extracellular immunoglobulin domains, a transmembrane domain and an intracellular domain. It is a pattern recognition receptor that can bind diverse ligands. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. It is found that calgranulin binding to the C1C2 domain or AGEs binding to the V domain activates extracellular signaling, which triggers interactions of …

A Laser-Pulse Photolysis Study Of The Mechanism Of Potentiation Of The Glua2qflip Ampa Receptors By Cx546, Yu-Chuan Shen

Legacy Theses & Dissertations (2009 - 2024)

Insufficient activity of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate ion channels is involved in neurological disorders and developmental problems, such as schizophrenia, one of the most serious psychiatric diseases. Use of regulatory agents to enhance AMPA receptor activity under the circumstance has been shown therapeutically beneficial. Specifically, small-molecule compounds generally termed as potentiators or positive modulators of AMPA receptors have long been pursued as drug candidates for a potential treatment of these neurological disorders and diseases. The goal of my MS thesis work is to investigate the mechanism of potentiation on AMPA receptor by a classic potentiator known as CX546. The …

A Kinetic Study Of Regulation Of Glua1 Homomeric And Heteromeric Ampa Receptors By 2,3-Benzodiazepines, Yin-Shuo (Andrew) Wu

Legacy Theses & Dissertations (2009 - 2024)

AMPA receptors are a subtype of the ionotropic glutamate receptor family. They are ligand-gated or glutamate-activated, transmembrane ion channels that mediate the majority of excitatory synaptic transmission in the central nervous system. AMPA receptors are essential for neuronal development and brain functions, including learning and memory. Over-activation of calcium permeable AMPA receptors has been linked to some neurological diseases such as stroke, Alzheimer’s disease and amyotrophic lateral sclerosis. Inhibitors of glutamate receptors are therefore drug candidates for the potential treatment of these neurological diseases. One of the most promising classes of AMPA receptor antagonists is 2,3-benzodiazepine derivatives, thought to be …

Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar

Wayne State University Theses

Number of small RNA (sRNA) gene regulators have mounted in E. coli over the years whereas the number of validated protein partners has not changed considerably. Hfq has remained the only well studied global regulatory partner of sRNAs in E. coli. However, direct or indirect involvement of other protein partners has always been speculated. Study from Blasi lab has shown that CsdA, one of the five DEAD-box RNA helicases of E. coli, is required for the DsrA mediated upregulation of rpoS under cold stress condition. Previous study from our lab has identified two other DEAD-box RNA helicases, RhlB and RhlE, …

Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett

Wayne State University Theses

Abstract

DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS

by

KHALIN NISBETT

May 2017

Advisor: Dr. Jeremy Kodanko

Major: Chemistry

Degree: Master of Science

Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …

Real-Time Investigation Of Bulky Lesion Bypass By Y-Family Dna Polymerase, Dpo4, Using Single Molecule Fret, Pramodha Liyanage

Wayne State University Dissertations

DNA is constantly exposed to various DNA damaging agents that are generated by various internal and external sources. Some of this damage may not be able to be repaired by cellular machineries causing DNA replication to be blocked. Once the replication fork is blocked by a DNA adduct, damage tolerance DNA polymerases, mainly Y-family, are able to restore the DNA replication by synthesizing past the DNA adduct. Benzo[a]pyrene (B[a]P) is one of the most studied environmental carcinogens. It is known to make covalent DNA adducts after metabolic activation and the bulkiness of the B[a]P adducts impose a strong barrier to …

Comprehensive Structural, Thermal And Toxicological Characterization Of 1-Ethyl-3-Methylimidazolium Alkylbenzenesulfonate Ionic Liquids, Hiranmayee Kandala

Electronic Theses and Dissertations

Synthesis and characterization of 1-ethyl-3- methylimidazolium alkylbenzenesulfonate ionic liquids for extraction of lignin from prairie cord grass have been studied. The ionic liquids (ILs) 1-ethyl-3- methylimidazolium benzenesulfonate (EBS), 1-ethyl-3- methylimidazolium toluenesulfonate (ETS) and 1-ethyl-3- methylimidazolium xylenesulfonate (EXS) have been synthesized in this research. An extensive structural, physical, thermal and toxicological characterization has been performed to understand the behavior of these ionic liquids. The reaction yield for the synthesis of EBS, ETS, and EXS ionic liquids was determined to be 91.2 ± 1.5 %, 96.1 ± 0.7 %, 99.0 ± 0.5 % respectively. Spectral analysis using NMR and FTIR confirms the …

Cbl And Cbl-B Dictate Csf-1r Endocytic Traffic And Signaling In Macrophages, Lu Huang

Electronic Theses and Dissertations

Macrophage colony stimulating factor receptor (CSF-1R or MCSFR) is a receptor tyrosine kinase essential for the growth and function of macrophages. Understanding the mechanisms that regulate CSF-1R activation and deactivation will provide insights to clinical treatment of macrophage related diseases including chronic inflammation and cancer. Previously, our laboratory showed that CSF-1R undergoes a novel membrane trafficking route that involves macropinocytosis to deactivate CSF-1R signaling. This thesis makes the discovery that the ubiquitin ligases Cbl and Cbl-b cooperate to regulate CSF-1R endocytosis and traffic to macropinosome in macrophages. Macrophages were derived from mice knocked out for Cbl, Cbl-b or the double …

Antimicrobial Activity Of Fractionated Borohydride-Capped And Electrochemical Colloidal Silver, Marjorie M. Markopoulos

Browse all Theses and Dissertations

Silver nanoparticles (AgNPs) and ionic silver (Ag+) are known to be broad-spectrum antimicrobial agents. Recent studies show these agents may be an alternative to the most widely used drinking water disinfectant, chlorine. Chlorine is a toxic industrial chemical with a lethal concentration of 430 ppm after 30 minutes. Additionally, chlorine can react with naturally occurring materials to produce a number of disinfection byproducts such as chloroform and trihalomethanes. Some of these byproducts pose cancer risks in addition to other negative impacts to human health. These would be eliminated with the use of Ag+ or AgNPs. The main goal of this …

The Maculoprotective Effect Of A Thiol Antioxidant In Retinal Degeneration Models, Hsiu-Jen Wang

Doctoral Dissertations

"Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among adults, age 60 and older, in developed countries. While oxidative stress is implicated in the pathogenesis of AMD, clinical studies have shown that dietary antioxidants can delay progression of AMD. Currently, there is no FDA-approved treatment for AMD. Therefore, we hypothesized that N-acetylcysteine amide (NACA), a thiol antioxidant, would protect retinal pigment epithelium and impede the progression of retinal degeneration. The goal of this work was to evaluate the efficacy of NACA in preventing retinal pigment epithelial cell and photoreceptor death in AMD models. To achieve this, we …

Investigating Medicinally Important Portein-Protein And Protein-Ligand Interactions : A Computational Approach, Cooper Ashley Taylor

Honors Theses

Molecular dynamics (MD) simulations and computational chemistry allow for an atomistic understanding of protein-protein and protein-ligand binding motifs. Through the use of MD, medicinally relevant complexes can be examined in detail unattainable by experimental methods. Within this work, systems pertinent to both Alzheimer’s Disease and HIV-1 are probed and thoroughly sampled to help elucidate potential therapeutic pathways. We used molecular dynamics and free energy estimations to gauge the affinity for the binary and ternary complexes of KLC1, APP and JIP1, three proteins all believed to be involved in the propagation of Alzheimer’s Disease. Two areas of thought exist suggesting that …

Complementary Charged Molecular Imprints Of West Nile Virus Antibodies, Julio Rincon

Open Access Theses & Dissertations

There is a significant demand for robust and stable receptor molecules that can mimic biological molecules, such as antibodies. Relying only on natural recognition molecules have greatly limited the uses and capabilities of many aspects of health sciences due to product expense and stability. This is especially important in medically underserved areas where the lack of resources and faulty or limited cold-chain makes antibody based diagnostics very difficult to implement.

With molecular imprinting, it is possible to recognize diseases with the added advantage of product stability, long term use, fast preparation and ease of scalability, all while being cost effective. …

Oxidative Stress And Proteomic Studies Of Mammalian Models Of Age-Related Metabolic Dysfunction In Neurodegenerative Disorders, Aaron M. Swomley

Theses and Dissertations--Chemistry

Expression proteomics is the field of science wherein proteins that make up the cellular proteome are identified both by name and by fold-change. Depending on the application of proteomics, this change in level could be due to internal cellular stressors or introduction of xenobiotics. Global oxidative stress measures use immunohistochemistry to determine the relative level of oxidative stress of macromolecules within the cell. In this dissertation, both global oxidative stress measures and expression proteomics were used in a variety of mammalian models in order to determine the effects of protein upregulation, intranasal insulin administration, and resveratrol supplementation on the cellular …

Synthesis And Development Of Zwitterionic Pei (Zpei) For Optimized Delivery Of Nucleic Acids, Joseph Raleigh Duke Iii

Theses and Dissertations--Chemistry

Gene therapy holds promise for the treatment a wide range of diseases ranging from cystic fibrosis to cardiovascular disease to cancer. The need for safe and efficient gene delivery methods remains the primary barrier to human gene therapy. Non-viral vector materials, including polymers, can be designed to be biocompatible and non-immunogenic, but lack the efficiency to be clinically relevant. Gene therapy awaits the development of new materials that are both safe and efficient. Here, we have synthesized a series of modified zwitterionic polymers based on the common transfecting agent polyethylenimine (PEI). Using a variety of biochemical and biophysical methods we …

Effects Of Silvopasture Establishment On Aqueous And Gaseous Soil N Losses At The University Of New Hampshire Organic Dairy Research Farm, Kathryn Ann Slebodnik

Honors Theses and Capstones

The expansion of local agriculture in the New England region is putting increased pressure on farmers to expand their arable land base. While clear-cutting is a traditional method of converting forested land to agriculture, it is known for having adverse ecological impacts. To minimize these impacts, farmers can create a silvopasture which incorporates a portion of the original forest canopy into pastures or crop fields. This study evaluates the impact of land-use changes for agriculture on soil nitrogen (N) retention. In particular, this study investigates the differences in soil N turnover, gaseous loss, and aqueous loss among an established forest, …

Do Elevated Levels Of Glutathione Decrease The Toxicity Of Plasticizers In Mouse Liver Cells?, Khatoon Albahrani

All Master's Theses

Phthalates are esters of phthalic acid that play a crucial role in the manufacturing industries for enhancing the properties of plastic materials. Di-(2-ethylhexyl) phthalate (DEHP) is one of the most common phthalates used in a variety of products including food packaging and medical equipment. Their use has caused public health concerns because of their toxic effects on reproductive and developmental processes. This study aims to investigate the response of two mouse hepatoma cell lines to the effects of DEHP and its bioactive metabolite mono (2-ethylhexyl) phthalate (MEHP). Cells were exposed to four concentrations (10, 50, 100, and 300 µM) of …