Medicine and Health Sciences Commons^™

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) …

Binding Interactions Of Biologically Relevant Molecules Studied Using Surface-Modified And Nanostructured Surfaces, Palak Sondhi

Dissertations

This research focuses on the field of surface nanobioscience, wherein different nanosurfaces that will be used as working electrodes in the electrochemical cell are manufactured and surface modified to understand the critical binding interactions between biologically significant molecules like proteins, carbohydrates, small drug molecules, and glycoproteins. This research is essential if we are to determine whether a synthetic molecule can serve as a therapeutic candidate or diagnose a disease in its early stages. In order to fully understand the binding interactions, the study begins with defining some of the fundamental concepts, principles, and analytical tools for biosensing.

Afterwards, we addressed …

Dynamic Regulation Of Store-Operated Calcium Entry By Protein S-Acylation, Goutham Kodakandla

Theses and Dissertations

Calcium plays a pivotal role in many physiological functions in cells. Cytosolic calcium levels are finely tuned by calcium ion channels, pumps, and intracellular organelles. Store-operated calcium entry (SOCE) is when depletion of endoplasmic reticulum (ER) calcium stores activates a calcium sensor known as stromal interaction molecule 1 (STIM1). Activation of STIM1 leads to a conformational change from a compact state to an extended state. This extended state of STIM1 allows it to bind to a calcium channel in the plasma membrane (PM) known as Orai1. The binding of Orai1 and STIM1 leads to opening of Orai1 channels and calcium …

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …

Computational And Experimental Investigation Of Elemental Sulfur And Polysulfide, Jyoti Sharma

Dissertations

Petroleum processing results in the generation of significant quantities of elemental sulfur (S₈), leading to a surplus of sulfur worldwide. Despite its abundance and low cost, the use of sulfur in value-added organic compound synthesis is limited due to its unpredictable and misunderstood reactivity. This dissertation aims to address this issue by tackling it from two angles. Firstly, by utilizing Density Functional Theory (DFT) calculations, the reactivity of sulfur in the presence of nucleophiles is studied. This facilitates the identification of organic polysulfide intermediates that can be generated under different conditions, as well as the corresponding reactivity for …

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 …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

Computer-Aided Drug Design Of Bakuchiol-Inspired Lxrα Modulators Against Acute Lymphoblastic Leukemia, Dillon P. Cao

LSU Master's Theses

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, accounting for approximately 25% of pediatric malignancies. Although glucocorticoids are commonly used to treat ALL, prolonged use can lead to steroid resistance, rendering the drug regimen ineffective. Therefore, alternative treatment avenues are needed for high- risk pediatric patients that do not respond well to traditional regimens.

Liver X Receptor α (LXRα) is presented as a potential alternative drug target for pediatric patients that exhibit suboptimal response to glucocorticoids. Limitations of the current LXRα modulators such as indiscriminate isoform selectivity between LXRα and LXRβ and consequent adverse effects …

Artemisinin And Its Derivatives Reactions: Characterization Of The Reaction Products Using Lc/Tof Ms, Kogila Vijayan

Theses and Dissertations

Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug with potential anticancer properties. In this work, LC/TOF MS was used to investigate the reaction of ART with DNA bases and estradiol. ART-deoxyadenosine and ART-deoxycytidine interactions were studied in the presence of Fe (II) ions. ART-deoxyadenosine and ART-deoxycytidine reaction mixtures gave chromatographic signatures that remained unchanged at room temperature but grew after incubation at 37°C. The change in temperature from room temperature to 37°C was the main driver of adduct formation in these reactions. ART was found to react with Fe (II) ions as observed from several new chromatographic …

Photoisomerizable Membrane Active Peptides, Cristina Ventura

Seton Hall University Dissertations and Theses (ETDs)

Membrane active peptides (MAPs) bind and partition into the cell membrane thus causing permeabilization. Many α-helical membrane active peptides contain central proline residues that distinguish the hydrophobic and hydrophilic faces of the helix. The proline induces a bend that produces a helix-hinge-helix motif. Mutation of these proline residues has a significant effect on the activity of the MAP. Azobenzene is a photoisomerizable molecule that switches from its trans to cis isomer upon excitation with ultraviolet (UV) light and from its cis to trans isomer upon excitation with visible light (VL). In this work it is hypothesized that the hinge function …

Photodynamic Therapy Agents: The Power Of Mjöllnir To Eradicate Cancer, Sidney M. Hopper

Honors College Theses

After its discovery back in the 1900s, photosensitizers became a critical study for potential treatments and cures for medical issues, including cancer. It was discovered that porphyrins appeared to target and accumulate in proliferating cells, and to reach the cells, a certain wavelength of light with maximum absorbance associated with the porphyrin was necessary to achieve cell death. Photodynamic therapy involves making use of porphyrins or metalloporphyrins as activators when exposed to such light. When activated, these compounds generate reactive oxygen species (ROS), such as HO- or O2-, which can react with nucleic acids found in DNA and RNA. In …

Utilizing Ultra-Performance Chromatography High-Resolution Mass Spectrometry To Investigate Fatty Acid Mediated Antibiotic Tolerance, Brittni Woodall

Doctoral Dissertations

The lipid membrane is the first component necessary to sustain life. To maintain homeostasis, segregate cellular machinery, provide protection from the environment, and reproduce, an organism must establish a boundary in which the processes can occur. Throughout the last two decades, research has propelled our knowledge of lipid membranes much beyond original hypotheses. Once thought of to be static and uniform, the understanding of the lipid membrane has evolved to encompass a structure that is responsive, unique, and intricately constructed by the organism itself. By chance or by choice, organisms adapt the lipid membrane according to the environment for which …

Excitation Power Dependence Of Blinking In Copper-Indium-Sulfide Quantum Dots, Nicholas Chambers

Physics Undergraduate Honors Theses

Under continuous excitation, quantum dots exhibit random transitions between fluorescent ON states and non-fluorescent OFF states --- a phenomenon known as blinking. A physical description of the mechanism responsible for blinking that applies broadly to many types of quantum dots remains under debate. We study the blinking behavior of the non-toxic CuInS2 quantum dot, a system that has seen little investigation at the single-particle level. In particular, the optical properties of CuInS2 quantum are often improved by adding ZnS to the nanoparticles, but this addition leads to complex structural-optical property relationships that are even less understood. To probe the relationship …

Anxiety-Like Behavior In C57bl/6j Mice Is Sexually Dimorphic And Altered By Buprenorphine, Ohm Sharma

Chancellor’s Honors Program Projects

No abstract provided.

Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li

McKelvey School of Engineering Theses & Dissertations

Neutrophil extracellular traps involve the rapid translocation of DNA to the outside of the cell under certain stimuli. This structure forms a fibrous network that is able to limit the spread of pathogens and to kill microorganisms. It has also been shown to be present in various pathological processes such as inflammation, autoimmune diseases, and cancer metastasis. Currently, the formation process of NETs in vivo is being extensively studied. However noninvasive detection and quantitation has yet to be achieved. A class of PET tracers are described here that consists of a DNA dye as the backbone that is labeled with …

Development Of Surface-Modified Liposomes For Drug Delivery Applications, Megan Louise Qualls

Doctoral Dissertations

Liposomes are spherical vesicles composed of a lipid bilayer membrane that assembles around an internal aqueous core. This duality gives liposomes the ability to encapsulate both hydrophobic cargo within the lipid bilayer and hydrophilic cargo in the aqueous core, making them versatile molecular carriers for drug delivery. Liposome platforms have many advantages and are promising drug delivery carriers, and research is ongoing to improve their designs for continued clinical applications. Many liposome types have been developed, but further work is needed to improve surface modification, site-specific targeting, and triggered cargo release in order to further the therapeutic applications of these …

Apkcs Role In Neuroblastoma Cell Signaling Cascades And Implications Of Apkcs Inhibitors As Potential Therapeutics, Sloan Breedy

USF Tampa Graduate Theses and Dissertations

Neuroblastoma (NB) is a cancer that develops in the neuroblasts. It is the most common cancer in children under the age of 1 year, accounting for approximately 6% of all cancers. The prognosis of NB is linked to both age and degree of cell differentiation. This results in a range of survival rates for patients, with outcomes ranging from recurrence and mortality to high survival rates and tumor regression. Our previous work indicated that PKC-ι promotes cell proliferation in NB cells through the PKC-ι/Cdk7/Cdk2 cascade. We report on two atypical protein kinase inhibitors as potential therapeutic candidates against BE(2)-C and …

Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage

Dissertations, Theses, and Capstone Projects

Nano-scale materials have gained much attention during the past few decades due to the stark differences in their properties compared to bulk material. Thus, they are being studied for a myriad of applications ranging from harnessing solar energy to diagnostics. This thesis focuses on the synthesis of hollow iron oxide nanoparticles using Galvanic replacement reactions and their application in drug delivery. Moreover, the use of a peptide precursor for the enhancement of exosomes is also discussed.

Chapter 1 discusses a simple and economical Galvanic approach used for the synthesis of hollow one-dimensional iron oxide nanotubes. In the initial reaction, the …

Split Catalytic Probes For The Detection Of Monkeypox Virus, Jaehyun Ahn

Honors Undergraduate Theses

The COVID-19 outbreak highlighted the important role that diagnostic tests play in the healthcare system. To reduce the impact of infectious disease outbreaks, the development of rapid and cost-effective point-of-care-tests (POCTs) is crucial. With the dissemination of the Monkeypox (Mpox) virus, it became a necessity to produce POCTS that are inexpensive and easy to use. This work explored the construction of two colorimetric assays that aim to detect Mpox genetic signatures. One is based on the split-peroxidase-like deoxyribozyme probes (sPDz), while the other utilizes a cascade system of split RNA-cleaving deoxyribozyme (sDz) and peroxidase-like deoxyribozyme (PDz). Both rely on catalytic …

Autodocking Studies Of Oxygenated Fullerenes As Inhibitors Of The Hiv Protease, Michael Kaminski

All Student Theses

In a previous study, several oxygenated fullerene compounds were produced by ozonation of C60 (Buckminsterfullerene) and were identified by elemental analysis and by SALI (surface analysis by laser ionization). Some of these compounds, especially a batch, SK-5, a mixture of C60O1-8, were shown to inhibit activities of HIV-Protease with IC50 (concentration for 50% inhibition) of 1 mg/mol in the in-vitro studies. The oxygenated fullerenes were shown to have epoxide, ketones, and hydroxyl functionalities. As expected, C60 interacted with ozone with alkene functionality and not as an aromatic compound. It was postulated that C60O had epoxide functionality, as a product of …

Deposited Cigarette Smoke As A Driver Of Oxidation And Partitioning Processes On Indoor Surfaces, April Hurlock

Honors Theses

Despite the large amount of time that individuals spend indoors during their lives, very little attention was paid to the chemistry that occurs on indoor surfaces until recently. Although not visible to the naked eye, physical and chemical processes, such as partitioning and oxidation, are occurring on virtually every indoor surface in a typical household. Indoor pollutants, ranging from skin oils to environmental cigarette smoke, drive a lot of these processes. The transformation of indoor surfaces by indoor pollutants can increase chemical exposure risks as new irritants or carcinogens can be introduced to the surfaces. In this thesis, I describe …

Development And Praxis Of Ph Drug Delivery System Contra Zika, Julissa Rodriguez

Electronic Theses and Dissertations

As the effects of global warming continue to spread throughout the world, another critical issue is slowly gaining attention in many urban tropical countries. The Emerging Infectious Diseases/ Pathogens list from the National Institutes of Health (NIH) listed the Zika virus as a potential pandemic threat. In 2015, an outbreak of Zika was noted in several South American countries until the spread reached an all-time high of 87 countries in 2017. During the outbreaks, adults affected were noted to have joint and muscle pains, fevers, and rashes. The worst cases reported would ultimately lead to Guillain-Barre symptoms. Still, pregnant women …

The Discovery And Characterization Of Novel Potent 5-Substituted 3, 3’, 4’, 7-Tetramethoxyflavonoid Dna Triplex Specific Binding Ligands, Vanessa Marie Rangel

University of the Pacific Theses and Dissertations

Chemotherapy works by killing fast dividing cells. Unfortunately, these drugs are not specific to cancer tissue and can damage normal cells. Chemotherapy is like taking poison and hoping it kills the cancer cells before it kills you. As an alternative, many researchers have investigated the use of antigene therapy to selectively target cancer causing genes to avoid off target effects. Although promising, the theory is limited by the stability of the triplex structure. Here, we report the discovery of potent triplex binding ligands derived from the natural product quercetin. Chemical derivatives of 5-substituted 3, 3’, 4’, 7-tetramethoxyquercetin derivatives were characterized …

Analysis Of Multi-Drug Resistant Mycobacterium Tuberculosis Using Split Deoxyribozymes, Abryana Fergus

Electronic Theses and Dissertations, 2020-

Globally, tuberculosis, a disease caused by the species of Mycobacterium tuberculosis (Mtb) complex, stands as a leading cause of death from a single infectious agent. Even though antituberculous drugs are available, treatment is challenging due to antibiotic resistance associated with point mutations in the bacterial genome. Resistance to the first-line antibiotics – rifampin and isoniazid – results in multidrug-resistant tuberculosis (MDR) requiring a more complicated treatment regimen. Timely and accurate identification of drug-resistant TB cases can help prescribe the most effective treatment and prevent the spread of infection. This research aims to develop an assay to discern multi-drug resistant forms …

Using Wastewater-Based Epidemiology To Study Chlamydia Occurrence On A College Campus, Jessie E. Chin Quee

Honors Undergraduate Theses

Chlamydia is a sexually transmitted disease caused by Chlamydia trachomatis, commonly affecting sexually active college-aged adults. Presently, opportunistic testing, self-testing, and information campaigns are methods to screen vulnerable populations and raise awareness about chlamydia. Chlamydia remains underdiagnosed and undertested due to a lack of participation by individuals who may have been exposed to it. Wastewater-based epidemiology is a rising biomonitoring tool that detects the presence of disease- and drug-specific biomarkers in a community's wastewater. In this study, wastewater-based epidemiology was used to detect the presence of C. trachomatis on the University of Central Florida campus. Wastewater samples were collected …

Cultivating Health, Not Wealth In The United States' Healthcare System: Comprehensive Revisions For The Orphan Drug Act Of 1983, Kayla Smith

Regis University Student Publications (comprehensive collection)

This thesis explores the way in which the Orphan Drug Act of 1983, originally instituted in response to a lack of treatments for rare diseases in the United States of America, has failed to achieve its initial objectives in the 40 years since its implementation. In evaluating various successful examples of government subsidization programs designed to intervene in private industry, this thesis composes the criterion required for funding-based legislation which maximize market outcomes while minimizing tax-payer burden. An analysis of the synthetic organic chemistry industry – and a case study into the production of a particular orphan treatment for a …

Application Of Mass Spectrometry For The Characterization Of Synthetic Oligomers And Natural Lignin, Poorya Kamali

Theses and Dissertations--Chemistry

As part of the ongoing effort to substitute finite fuel and chemical resources with renewable ones, biomass is emerging as one of the most promising sources. Biomass consists of three main components of cellulose, hemicellulose, and lignin. Traditionally, cellulose has been used extensively in pulping industry, while lignin has been considered waste and is burned to generate heat. Lignin, a complex aromatic polymer component of biomass, has the potential to be used as a source of aromatic chemicals and pharmaceutical synthons. The recalcitrant nature of lignin, the lack of effective lignin breakdown methods and analytical techniques to analyze it are …