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Synthesis, Characterization And Biological Studies Of Technetium-99m And Rhenium-188 Peptides, Vanessa Anne Sanders

UNLV Theses, Dissertations, Professional Papers, and Capstones

Radiopharmaceuticals are very powerful diagnostic tools for evaluation of a host of medical conditions. These drugs are labeled with radioactive isotopes, which are utilized to create pictures of areas of interest through absorption of the drug. They are currently in high demand due to their ability to image areas that traditional imaging devices cannot. The radioisotope 99mTc, with a half-life of 6.01 hours and a 140 keV gamma emission, is central to many radiopharmaceutical compounds. This isotope is easily obtained from a 99Mo-99mTc generator, through beta decay and column chromatography separations. Very little technetium, less than 6 ng, is needed …

Conformational Studies Of A Domain Of The Influenza A M2 Protein Involved In Viral Budding And Morphology, Alice L. Herneisen , '17

Senior Theses, Projects, and Awards

In my two years working in the Howard lab, I have cycled through a number of projects. These projects fall under the broad context of studying of how the cytoplasmic tail of a particular membrane protein of the influenza A virus, the Matrix protein 2 (M2), is involved in viral budding. I have chosen to present each project in the form of an independent manuscript, with separate Introduction, Experimental, Results, and Discussion sections. Some broader background and theory is briefly provided in Chapters 1 and 2, but Chapters 3-5 are designed to be largely self-contained. Potential future directions pertaining to …

Designing Proteins For Biomechanical And Molecular Biological Studies, Momoko Tajiri

TechTalks

Proteins are large biomolecules consisting one or more long chain of amino acid residues. Proteins perform a wide variety of functions within organisms including catalyzing metabolic activities, signal transduction, and transportation of molecules. They function differently from one another as their sequences of amino acids and also due to a variation of modification placed on residues. Change in modification patterns will impact protein interaction with other molecules, thus influence normal cell activities and may lead to disease development. In order to study the consequences of modification, we have a method to prepare proteins with desired modification patterns. Using the technique, …

Synthesis And Reactivity Of Sydnone Derived 1,3,4-Oxadiazol-2(3h)-Ones, Jonathan Michael Tumey

Browse all Theses and Dissertations

5-(Bromomethyl)- and 5-(trichloromethyl)-3-phenyl-1,3,4-oxadiazol-2(3H)-ones were synthesized from bromocarbonyl hydrazine intermediate salts and acid halides to provide further evidence for our proposed mechanism for the formation of oxadiazolone ring systems from sydnones. 5-(Bromomethyl)-3-phenyl-1,3,4-oxadiazol-2(3H)-one was a compound of interest due to its SN2 possibilities and three potential sites of diversification. The procedure to synthesize 5-(bromomethyl)-3-phenyl-1,3,4-oxadiazol-2(3H)-one was developed originally by Madaram in the Turnbull lab, but was further optimized in the present work by altering the time, temperature and stoichiometric equivalents of the acid halide to provide high purity and excellent yields of the product. While this compound of interest had been isolated and …

Design, Synthesis And Biological Evaluation Of Novel Estradiol-Triazole Analogs Targeting Epidermal Growth Factor Receptors In Colorectal Cancer, Faez Alotaibi

Electronic Theses and Dissertations

Colorectal cancer is a life threatening and second cause of death from cancer in the United States. Several proteins (molecular targets) are highly expressed in Colorectal cancer (CRC). Among these molecular targets is Epidermal Growth Factor Receptors (EGFRs) which are overexpressed in cancer cells. Targeting and blocking the downstream signaling could lead to cease cell proliferation and division and hence control the spread of the disease. Molecular modeling is a powerful tool in drug discovery, which has been utilized to design many drug candidates that exhibit biological effect in many disease including cancer. Additionally, pharmacophores such as 1,2,3-triazole showed potency …

Advanced Analytical Strategies To Determine Biomedical Parameters For Medical Diagnostics, Drug Delivery, And Therapy, Sisi Chen

Doctoral Dissertations

"Biomedical parameters are critical for diseases prognosis, diagnosis and therapy. Many research groups have dedicated their studies to develop analytical instrumentation and apply analytical methods to determine biomedical parameters that have the potential to help with disease control and increase public health. This dissertation focuses on three major aspects of analytical strategies development and applications: 1) detection of pH changes caused by nanotoxicity (induced by TiO₂ nanoparticles) using newly developed micro-pH sensor, 2) quantification of renal cell carcinoma (RCC) biomarkers by high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS), and 3) nuclear magnetic resonance (NMR) studies of porous wall …

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 …

Bodipy-Based Red Sensitizers For Near-Infrared Emission Of Lanthanide Complexes, Priyangika Prasadini Senevirathne

Masters Theses

During the past 20 years there has been a remarkable growth in the use of the fluorescence technique in biological studies. Fluorescence and time-resolved fluorescence spectroscopy are considered primary research tools in the field of biochemistry. Currently, fluorescence spectroscopy is a dominant methodology and used widely in biotechnology and medical diagnosis process. One impediment in using fluorescent probes is the fluorescence of biological substrates and fluorescence of diagnostic probes are significantly overlapped, and it decreases the detection sensitivity. Also, commercially available probes require UV or near-UV light excitation, causing severe degradation of biological substrates. Near-infrared emitting lanthanide complexes can overcome …

Design And Synthesis Of Selenium Nanoparticles To Overcome Multiple Drug Resistance Of Cancer Cells, Urarika Luesakul

Chulalongkorn University Theses and Dissertations (Chula ETD)

The objective of this research is to synthesize selenium nanoparticles (SeNPs) stabilized by chitosan as a drug carrier for delivery doxorubicin to overcome drug-resistant in cancer cells. One important mechanism of multidrug resistance (MDR) includes decreased drug influx and increased drug efflux, leading to insufficient drug concentration to kill cancer cells. Therefore, to overcome MDR by increasing cellular uptake, the surface of SeNP was functionalized to provide 3 structural features: (i) a positive charge to improve their solubility, (ii) gallic acid, a hydrophobic molecule to enhance biocompatibility and (iii) folic acid, a targeting molecule to target cancer cells and enhance …

Synthesis Of Cationic Cdse/Zns Quantum Dots And Applications In Dna Detection, Jamornpan Yangcharoenyuenyong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Semiconductor nanoparticles or quantum dots (QDs), especially CdSe/ZnS QDs, are of great interest in bioapplications due to their unique size-dependent optical properties and photo-stability. One of the plausible applications of QDs is DNA detection using QDs as a novel fluorescence tool for sensing of DNA using the electrostatic interaction between negative charge of DNA and positive charge on QDs surface. In this work, CdSe/ZnS QDs were synthesized using a hot-solution decomposition process resulting in hydrophobic CdSe/ZnS QDs. To obtain water-soluble and cationic QDs, the surface of QDs were modified with poly(ethylene)imine (PEI) via micelle formation. Because of hydrophilicity of PEI …

Biofunctionalized Capillary Flow Channel Platform Integrated With 3d Nanostructured Matrix To Capture Circulating Tumor Cells, Shashwat Banerjee, Ganesh Khutale, Vrushali Khobragade, Narendra Kale, Milind Pore, Govind Chate, Archana Jalota-Badhwar, Manoj Dongare, Jayant Khandare

Articles

Circulating tumor cells (CTCs) from peripheral blood account genetic information for cancer diagnosis and overall disease monitoring. Analysis of “liquid biopsy” holds immense promise as it may lead to new approaches for cancer treatment. The study reports effective and continuous flow microchannel system for isolating CTCs using transferrin conjugated 3D matrix synthesized by crosslinking polyethylene glycol-Fe3O4 nanostructures for rapid and efficient capturing of CTCs. The platform provides option of using multiple microchannel units in series that can influence higher cell-capture efficiency due to increasing cell-substrate contact frequency. CTCs are captured with high efficiency even at low concentration of target cells …

Design, Synthesis, Characterization And Evaluation Of Near Infrared Bodipy Dyes For Various Applications, Qianli Meng

LSU Doctoral Dissertations

4,4-Difluoro-4-bora-3a,4a-diaza-5-indacene (BODIPY) have drawn a large number of research attention, for its numerous useful application in the fields of material and biology. Small modification of this well-known fluophore has been shown to optimize its photophysical and chemical properties. This work mainly focuses on functionalization of BODIPY cores with halogenated atoms, particularly iodine, and their subsequent post-functionalization reactions, mainly cross-coupling reaction and substitutions, for various further applications. Chapter 1 of this dissertation gives a general overview of BODIPYs including their synthetic strategies, post-functionalization, and how BODIPYs are utilized in many biological applications. Chapter 2 mainly focuses on the synthesis and characterization …

Human Serine Racemase Structure/Activity Relationship Studies Provide Mechanistic Insight And Point To Position 84 As A Hot Spot For Β-Elimination Function, David L. Nelson, Greg A. Applegate, Matthew L. Beio, Danielle L. Graham, David B. Berkowitz

Department of Chemistry: Faculty Publications

There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist D-serine. Reported correlation of D-serine levels with disorders including Alzheimer’s disease, ALS, and ischemic brain damage (elevated D-serine) and schizophrenia (reduced D-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser⁸⁴, the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of L-serine over the normally preferred L-serine-O-sulfate (~1200-fold change in k_cat/K_{m …}

Nitroxide-Based Macromolecular Contrast Agents With Unprecedented Transverse Relaxivity And Stability For Magnetic Resonance Imaging Of Tumors, Hung V.T. Nguyen, Qixian Chen, Joseph T. Paletta, Peter Harvey, Yivan Jiang, Hui Zhang, Michael Boska, M. Francesca Ottaviani, Alan Jasanoff, Andrzej Rajca, Jeremiah A. Johnson

Andrzej Rajca Publications

Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxidefunctionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous …

A Simplified Direct Lipid Mixing Lipoplex Preparation: Comparison Of Liposomal-, Dimethylsulfoxide-, And Ethanol-Based Methods, Joseph Meisel, George Gokel

Chemistry & Biochemistry Faculty Works

Established transfection methodology often uses commercial reagents, which must be formed into liposomes in a sequence of about half a dozen steps. The simplified method reported here is a direct lipid mixing approach that requires fewer steps, less manipulation, and is less time-consuming. Results are comparable to those obtained with more commonly used methods, as judged by a variety of analytical techniques and by comparisons of transfection results. The method reported here may be applied to non-liposome-forming compounds, thereby greatly expanding the range of structures that can be tested for transfection ability.

Synthesis Of Simplified Ym-254890 Analogs, Derek Thomas Rensing

Arts & Sciences Graduate Student Theses and Dissertations

G Protein Coupled Receptors (GPCR’s) are responsible for a multitude of physiological, cellular, and disease processes. GPCR’s signal through non-receptor based heterotrimeric G proteins and since G proteins effectively mediate GPCR signal transduction they are attractive therapeutic targets. However, little is known about the signaling pathways associated with individual G proteins. For this reason, there is intense interest in the development of chemical probes that can help identify the downstream biochemistry of individual G proteins.One small molecule natural product that shows promise along these lines is YM-254890 (YM). YM has been shown to specifically and potently inhibit the α subunit …

Synthesis And Characterization Of Amphiphiles For Mammalian Cell Transfection And Antimicrobial Activity, Joseph William Meisel

Dissertations

Amphiphiles are molecules that contain both water-soluble and water-insoluble components. The dual nature of these molecules engenders remarkable properties including the ability to self-assemble into ordered structures. Cell membranes are composed of amphiphilic phospholipids that organize into a bilayer motif. Synthetic amphiphiles can interact with natural membranes and influence the transport of molecules across the cell membrane. The work elaborated in this report employs amphiphiles to co-assemble with DNA and transport the genetic material across cell membranes. First, a simplified method for interacting DNA with amphiphiles was developed. Second, a series of known ion-transporting compounds were assayed for their interaction …

Studies On Purification And Functionalization Of Carbon Nanotubes And Their Aqueous Phase Behavior, Zheqiong Wu

Dissertations

Carbon nanotubes (CNTs) are known to have unique mechanical, thermal and electrical properties which make them attractive for a wide range of applications ranging from batteries to sensors. CNTs are rolled up graphene sheets where the single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs) are classified according to the number of concentric rings. In this dissertation, the focus is on several different aspects of MWCNTs. These include purification, functionalization and colloidal behavior.

MWCNTs are insoluble in solvents and therefore some degree of functionalization is required prior to their real-world applications. Oxidation debris is generated during carboxylation which is usually the first …

The Effect Of Hofmeister Series Counterions On The Colloidal And Antimicrobial Properties Of Triple-Headed Cationic Amphiphiles, Kirstie A. Thompson

Senior Honors Projects, 2010-2019

Antibacterial resistance is becoming increasingly prominent, causing a great need for novel antibacterial products. This work focuses on developing an understanding of the relationship between counterion identity on colloidal and antibacterial activity for cationic amphiphiles. In an amphiphile series with three hydrophilic quaternary ammonium bromide head groups and one hydrophobic tail, the amphiphile with a linear hydrocarbon chain with 18 carbons is more antibacterial than those with longer or shorter tails. Counterion exchange of the bromide counterions with various Hofmeister series anions significantly affects both antibacterial and colloidal activity. The logarithm of critical aggregation concentration [log(CAC)] was found to have …

Photochemical Electrocyclic Ring Closure And Elimination Reactions Of N-(Oxothioxanthenyl)Naphthothiophene Carboxamides, Himali Devika Jayasekara

Dissertations (1934 -)

Photochemical cleavage reactions have found a widespread used in biological applications that require the photorelease of biologically active molecules such as proteins, peptides, neurotransmitters, and nucleotide phosphates. This research focuses on the design of photoremovable protecting groups which can be utilized to release these biomolecules by photolysis. These biomolecules are attached to the photoremovable protecting group at the sites of functional groups that are present within these substrates. Such functional groups are carboxylates, phosphates, thiolates, or phenolates, which upon exposure to light, are released as anions of varying basicities. The photochemical reaction involved is an electrocyclic ring closure between aromatic …

Synthesis And Mechanistic Investigations Of Transition Metal Complexes And Ligands For Chemotherapeutic Applications, Jimmie Lee Bullock Jr.

Chemistry & Biochemistry Theses & Dissertations

Transition metal complexes have played a critical role in antitumor therapy with many complexes incorporating platinum, ruthenium, and lanthanum having been investigated in preclinical and clinical trials. The best known transition metal therapeutic is cisplatin, which is utilized in nearly 50% of all cancer therapies, despite its significant toxic side effects. The toxic side effects of current FDA approved platinum-based chemotherapeutics are often overlooked due to the “special status” granted to these drugs due to their ability to fight, what is often considered an incurable disease with life expectancies often measured in months. Oncology drug development has therefore now focused …

Novel Photodynamic Cancer Therapy Agent And Biochemical Phosphate Sensor Based On Nanomaterials, Alaa Fadhel

Electronic Theses and Dissertations

Biochemical research and clinical studies have revolutionized the field of medicine in both diagnosis and therapy. Researchers in the field of biochemistry and biotechnology are using nanomaterials in different applications to develop devices and materials that offer benefits to both patients and the health care industry. These include biochemical sensors, enzyme encapsulation, biomarkers, and drug delivery improvements for the treatment of cancer. This dissertation focuses on investigating two biochemical aspects using nanomaterials; namely therapy and clinical diagnosis. For therapy purposes, Silica nanoparticles were used as drug delivery system to develop a new photodynamic cancer therapy agent photo-acid generator (PAG) that …

Characterization Of An Al$^{3+}$-Selective Fluorescent Probe Based On A Benzoyl Hydrazine Derivative And Its Application In Cell Imaging, Yuxiang Ji, Chunwei Yu, Shaobai Wen, Jun Zhang

Turkish Journal of Chemistry

A fluorescent probe based on benzoyl hydrazine was synthesized and characterized as an Al$^{3+}$-selective fluorescent probe. This probe showed good selectivity towards Al$^{3+\, }$compared to other common ions. Under optimized experimental conditions, the probe exhibited a linear dynamic response for Al$^{3+}$ from 5.0 $\times $ 10$^{-7}$ to 4.5 $\times $ 10$^{-6}$ M with a detection limit of 1.3 $\times $ 10$^{-7}$ M in ethanol-water solution (9:1, v:v, pH 6.8, 20 mM HEPES). Furthermore, it was used for imaging of Al$^{3+}$ in living cells with satisfying results.

An In Vitro Study On The Effect Of Synthesized Tin (Iv) Complexes On Glioblastoma, Colorectal, And Skin Cancer Cell Lines, Jennie L. Williams, Lesley C. Lewis-Alleyne, Melinda Solomon, Long Nguyen, Robert Johnson, Jennifer Vital, Ping Ji, John Durant, Camille Cooper, Patrice Cagle, Patrick Martin, Don Vanderveer, William L. Jarrett, Alvin A. Holder

Chemistry & Biochemistry Faculty Publications

((E)-2-(2-hydroxybenzylideneamino)phenolato-2,2-diphenyl-6-aza-1,3-dioxa-2-stanna-[d,h]dibenzocyclononene, [Sn(Ph₂SB)] (compound 1, where Ph₂SB=(E)-2-(2-hydroxybenzylideneamino)phenolato Schiff base) and two novel compounds, [[SnPh2(F-azoSB)] (compound 2, where F-azoSB=4-((E)-(4-fluorophenyl)diazenyl)-2-((E)-(2-hydroxyphenylimino)methyl)phenolato Schiff base), [[SnPh2(sulf-azoSB)]0.125CHCl₃ (compound 3, where sulfamerazineazosalSB=4-((E)-(4-hydroxy-3-((E)-(2-hydroxyphenylimino)methyl)phenyl)diazenyl)-N-(4-methylpyrimidin-2-yl) benzenesulfonamide Schiff base), and the control compound, cisplatin (compound 4) were analysed to comparatively determine their effect on cancer cell growth. Anti-cancer properties of compounds 1-4 were examined using glioblastoma (U-1242 MG), colorectal (HT-29 and HCT-116), and skin (A431) human cancer cell lines. With regards to human glioblastoma cells, compounds 1 and 3 demonstrated anti-proliferative capacity in the cell line tested. Specifically, compounds 1 and 3 inhibited cell proliferation by 50% at …

Application Of Encoded Microparticles Fabricated By Standard Lithography On Multiplexed Bioassay, Muhan He

Legacy Theses & Dissertations (2009 - 2024)

Suspension microarray, has become a popular candidate for multiplexed bioassay since its advent. Unlike traditional planar microarray, suspension microarray permits the probes suspended in aqueous solution while keeping their addresses, and possesses many advantages such as large available binding surface, rapid reaction rate, high multiplexing ability, and high sensitivity and specificity. Photolithography, the technology widely utilized for production of abundant microparticles as carrier in suspension microarray, was investigated by many researchers. However, there was still not a mature, efficient method to produce microparticles with low background, easily recognized identity and good hybridization capacity. To address those issues, we developed a …

Design, Synthesis And Physicochemical Analysis Of Ruthenium(Ii) Polypyridyl Complexes For Application In Phototherapy And Nucleic Acid Sensing, Erin Melissa Wachter

Theses and Dissertations--Chemistry

Current chemotherapeutics exhibit debilitating side effects as a result of their toxicity to healthy tissues. Reducing these side effects by developing chemotherapeutics with selectivity for cancer cells is an active area of research. Phototherapy is one promising modality for selective treatment, where drug molecules are “turned on” when irradiated with light, reducing damage to healthy tissues by spatially restricting the areas exposed to irradiation. A second approach to improve selectivity is to exploit the differences in cancerous versus healthy cells, such as increased metabolism and/or upregulation of cell surface receptors. Ruthenium(II) polypyridyl complexes are candidates for phototherapy due to their …

Contemporary Organic Transformations Enabled By Novel Cationic Processes, Caitlan Elizabeth Ayala

LSU Doctoral Dissertations

This dissertation focuses on the development of synthetic methodologies in organic synthesis in two different areas. Chapter 1 discusses the more recent examples of transforming alcohols to their corresponding alkyl chlorides. The first area of our group’s research interest is the development of a mild chlorination method from unactivated alcohols, detailed in Chapter 2. Chapter 3 provides an insight into the history of oxyallyl cations, the basis of the second methodology development project in our laboratory. This chapter focuses on the traditional reactions that utilize these reactive intermediates, and it also showcases the concept of direct nucleophilic addition and the …

Synthesis And Characterization Of Cyclic Polypeptoids By Organo-Mediated Controlled Zwitterionic Ring-Opening Polymerization And Development Of Redox-Responsive Polypeptoid Micelles As Drug Delivery Carriers, Ang Li

LSU Doctoral Dissertations

Peptoids are peptidomimetic polymers, which have attracted much attention over the past two decades. They have similar building blocks to peptides, and the similarity makes the backbone of peptoids hydrophilic and biocompatible.1 Two types of peptoid polymers are under development. One is sequence-defined peptoids, which exhibit excellent bioactivities.2 Another one is polypeptoids. The good biocompatibility and highly tunable side chain substituents allow polypeptoids to be used broadly in future biomedical applications. Varying polymer architectures, including linear polymers, cyclic polymers, comb-like polymers, and dendrimers can provide distinctive properties to the polymers. Cyclic polymers employ a cyclic architecture and lack chain ends, …

Design, Synthesis And Biological Applications Of Polypeptoids And Boron Dipyrromethenes, Sunting Xuan

LSU Doctoral Dissertations

The dissertation is about the design, synthesis and biological applications of polypeptoids and boron dipyrromethenes (BODIPYs). The dissertation is divided into seven chapters reporting various aspects of the background to my field of study and the results obtained during my PhD program. Chapter 1 is a concise overview of the fundamental concepts of polypeptoids and hydrogels, as well as their recent developments on synthetic strategies, property investigations, and biological applications in different fields. Chapter 2 presents the design, synthesis and potential application as tissue engineering scaffold of thermoreversible ABC polypeptoid hydrogels. A series of ABC copolypeptoids were synthesized and their …

Manipulating Electron Transfer Reactions From Micro- To Preparative Scale, Matthew Duane Graaf

Arts & Sciences Graduate Student Theses and Dissertations

The utilization of electron transfer reactions has allowed the transformation of a variety of substrates from polymer surfaces to highly functionalized organic molecules. The intricacies of these electron transfer reactions have been utilized to develop a new platform for building and studying addressable molecular libraries as they interact with biological targets. As a low cost, reusable alternative to other methods of these studying binding interactions, microelectrode arrays are beginning to gain traction with the scientific community as we continually push the limits of their potential. Additionally, the electron transfer techniques used to build the molecular libraries can be expanded to …