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Oligodeoxynucleotide Synthesis Using Protecting Groups And A Linker Cleavable Under Non-Nucleophilic Conditions, Xi Lin

Dissertations, Master's Theses and Master's Reports - Open

Oligodeoxynucleotides (ODNs) containing latent electrophilic groups can be highly useful in antisense drug development and many other applications such as chemical biology and medicine, where covalent cross-linking of ODNs with mRNA, protein and ODN is required. However, such ODN analogues cannot be synthesized using traditional technologies due to the strongly nucleophilic conditions used in traditional deprotection/cleavage process.

To solve this long lasting and highly challenging problem in nucleic acid chemistry, I used the 1,3-dithian-2-yl-methoxycarbonyl (Dmoc) function to protect the exo-amino groups on the nucleobases dA, dC and dG, and to design the linker between the nascent ODN and solid support. …

Method Development Using Laser Ablation And Solution Icpms And Their Application In Environmental Science And Forensic Provenance Studies, Kaixuan Bu

Electronic Theses and Dissertations

Inductively coupled plasma mass spectrometry (ICPMS) is an analytical technique that can be used to determine multiple elements and isotope ratios in a wide variety of samples. In this work, four projects are described that involve the method development using laser ablation (LA) and solution-based ICPMS and their application in environmental science and forensic (provenance) investigations. In the first project, plutonium (Pu) concentrations and 240Pu/ 239Pu atom ratios were measured in kelp, lichen, aquatic moss, and horse mussel collected on or near Amchitka Island, a former nuclear test in Alaska, and at a background site. The Pu in terrestrial and …

Identification Of A Histidine Metal Ligand In The Arge-Encoded N-Acetyl-L-Ornithine Deacetylase From Escherichia Coli, Wade C. Mcgregor, Danuta M. Gillner, Sabina I. Swierczek, Dali Liu, Richard C. Holz

Chemistry: Faculty Publications and Other Works

The H355A, H355K, H80A, and H80K mutant enzymes of the argE-encoded N-acetyl-L-ornithine deacetylase (ArgE) from Escherichia coli were prepared, however, only the H355A enzyme was found to be soluble. Kinetic analysis of the Co(II)-loaded H355A exhibited activity levels that were 380-fold less than Co(II)-loaded WT ArgE. Electronic absorption spectra of Co(II)-loaded H355A-ArgE indicate that the bound Co(II) ion resides in a distorted, five-coordinate environment and Isothermal Titration Calorimetry (ITC) data for Zn(II) binding to the H355A enzyme provided a dissociation constant (K_d) of 39 μM. A three-dimensional homology model of ArgE was generated using the …

Investigation Of A Novel Magnesium And Acidified Ethanol System For The Degradation Of Persistent Organic Pollutants, Phillip Maloney

Electronic Theses and Dissertations

For centuries chemists have sought to improve humankind’s quality of life and address many of society’s most pressing needs through the development of chemical processes and synthesis of new compounds, often with phenomenal results. Unfortunately, there also are many examples where these chemicals have had unintended, detrimental consequences that are not apparent until years or decades after their initial use. There are numerous halogenated molecules in this category that are globally dispersed, resistant to natural degradation processes, bioaccumulative, and toxic to living organisms. Chemicals such as these are classified as persistent organic pollutants (POPs), and due to their negative environmental …

Identification Of A Histidine Metal Ligand In The Arge-Encoded N-Acetyl-L-Ornithine Deacetylase From Escherichia Coli, Wade C. Mcgregor, Danuta Gillner, Sabina I. Swierczek, Dali Liu, Richard C. Holz

Chemistry Faculty Research and Publications

The H355A, H355K, H80A, and H80K mutant enzymes of the argE-encoded N-acetyl-L-ornithine deacetylase (ArgE) from Escherichia coli were prepared, however, only the H355A enzyme was found to be soluble. Kinetic analysis of the Co(II)-loaded H355A exhibited activity levels that were 380-fold less than Co(II)-loaded WT ArgE. Electronic absorption spectra of Co(II)-loaded H355A-ArgE indicate that the bound Co(II) ion resides in a distorted, five-coordinate environment and Isothermal Titration Calorimetry (ITC) data for Zn(II) binding to the H355A enzyme provided a dissociation constant (K_d) of 39 μM. A three-dimensional homology model of ArgE was generated using the …

Synthesis Of The Western Hemisphere Of Theonellamide C, Saroj Yadav

LSU Doctoral Dissertations

Theonellamides A-F were isolated from Theonella swinhoei by Fusetani and co-workers. Despite considerable synthetic effort to produce theonellamide F by the Shioiri group in the early 1990’s, the total synthesis of a theonellamide has yet to be reported. We report herein our efforts toward some of the required amino acid residues and construction of the western ring of theonellamide C. We describe the synthesis of an uncoded amino acid, (2S,4R)-ɣ-hydroxy-α-amino adipic acid (Ahad), a building block for theonellamide C. We initially investigated the Corey-Lygo method for the catalytic asymmetric generation of the Cα stereocenter. Unfortunately, the alkylation of glycine benzophenone …

Polymer Microsystems For The Enrichment Of Circulating Tumor Cells And Their Clinical Demonstration, Joyce W. Kamande

LSU Doctoral Dissertations

Cancer research is centered on the discovery of new biomarkers that could unlock the obscurities behind the mechanisms that cause cancer or those associated with its spread (i.e., metastatic disease). Circulating tumor cells (CTCs) have emerged as attractive biomarkers for the management of many cancer-related diseases due primarily to the ease of securing them from a simple blood draw. However, their rarity (~1 CTC per mL of whole blood) makes enrichment analytically challenging. Microfluidic systems are viewed as exquisite platforms for the clinical analysis of CTCs due to their ability to be used in an automated fashion, minimizing sample loss …

Laser Ablation Sample Transfer For Mass Spectrometry, Sung-Gun Park

LSU Doctoral Dissertations

In this research, a new ambient sampling technique for mass spectrometry was developed that uses an infrared laser to ablate materials under ambient conditions that are captured in a solvent or on a surface. An infrared optical parametric oscillator (OPO) laser system at 3 μm wavelength was focused onto samples for ablation at atmospheric pressure. The ablated materials were transferred to a solvent or surface. For off-line electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) analysis, the ablated material was captured in a static solvent droplet that was deposited on a MALDI target or flow-injected into a nanoelectrospray source. The …

Oligomers Of Beta-L-Arabinosides Of Hydroxyproline : Synthesis Of The Carbohydrate Epitope Of The Art V 1 Allergen, Ning Xie

LSU Doctoral Dissertations

The pollen of mugwort is a major contributor to hay fever in Europe and North America. The chemical structure of Art v 1, the major allergen of mugwort, has been elucidated. A notable motif in Art v 1 – characterized by clusters of contiguous â-arabinosides of hydroxyproline – was found to be a key recognition element for antibodies generated in response to the natural protein. This dissertation details the chemical synthesis of oligomers of â-arabinosides of hydroxyproline and the search to establish the minimal carbohydrate epitope of Art v 1. The â-arabinoside motif, being a 1,2-cis glycoside, presents a considerable …

Surface Studies Of Organic Thin Films Using Scanning Probe Microscopy And Nanofabrication, Venetia Denae Lyles

LSU Doctoral Dissertations

Porphyrins and metalloporphyrins have unique chemical and electronic properties and thus provide useful model structures for nanoscale studies of the role of chemical structure for electronic properties. Porphyrins have been proposed as viable materials for molecular-based information-storage devices, gas sensors, photovoltaic cells, organic light-emitting diodes and molecular wires. The function and efficiency of porphyrins in devices is largely attributable to molecular architecture and how the molecules are self-organized. Modifications of the porphyrin macrocycle, peripheral groups or bound metal ions can generate a range of electrical, photoelectrical or magnetic properties. The conductive properties are greatly influenced at the molecular level by …

Method Development For A Chemical And Biological Analysis Of Glucocorticoids In Wastewater, Maria Carmen Lozano

Open Access Theses & Dissertations

Glucocorticoids are a class of steroid hormones that can either be produced synthetically or naturally by the adrenal glands. The synthetic glucocorticoids are highly prescribed in the United States for their anti-inflammatory and immunosuppressive properties to treat a variety of ailments and diseases; however, these have been implicated in a number of adverse human conditions such as obesity, metabolic syndrome, immune-suppression, delayed puberty, adrenal insufficiency and Cushing Syndrome, among others. Ongoing research has shown that synthetic and natural hormones are transported to aquatic environments via mammalian excretion or wastewater effluent, and as a result, the release of glucocorticoids into the …

Water-Soluble Deep-Cavity Cavitands: Synthesis, Molecular Recognition, And Interactions With Phospholipid Membranes, Sarah E. Ioup

LSU New Orleans Theses and Dissertations

Water-soluble deep-cavity cavitands provide a rare opportunity to study self-assembly driven by the hydrophobic effect. These molecular hosts dimerize in the presence of certain guest molecules to form water-soluble molecular capsules. These systems have given rise to numerous novel chemical phenomena and have potential use in drug delivery. The host octaacid (OA) has been particularly well-characterized, but studies are limited to basic pH because of limited host solubility.

Herein we report an improved synthesis of OA and the syntheses of three new water-soluble deep-cavity cavitands. The new hosts are soluble at neutral pH, increasing relevance for biological studies. The new …

Synthesis, Design, And Biological Evaluation Of Inhibitors And Activators Of Src Homology 2 Domain-Containing Inositol Phosphatase (Ship) And Synthetic Studies Of Apicularen A And Maoecrystal V, Dennis Racca Viernes

Chemistry - Dissertations

This dissertation involves work both on the syntheses of small molecules with potential therapeutic applications and synthetic studies on natural products with unusual core skeletons.

The first part of this work involves the synthesis, design, and biological evaluation of aminosteroids as inhibitors for the SH2-containing inositol phosphatase 1 (SHIP1). SHIP1, a 145 kDa protein, is involved in regulating the formation of new blood cells. High- throughput screening identified several SHIP inhibitors including NSC23922, a mixture of 3a- and 3β-aminocholestane. Both 3a- and 3β-aminocholestane were synthesized from dihdyrocholesterol and the 3a- form was verified as …

A Novel Microfluidic Enrichment Technique For Carbonylated Proteins, Bryant C. Hollins

Doctoral Dissertations

Proteins are the building blocks of cells in living organisms, and are composed of amino acids. The expression of proteins is regulated by the processes of transcription and translation. Proteins undergo post-translational modifications in order to dictate their role physiologically within a cell.

Not all post-translational modifications are beneficial for the protein or the cell. One type of post-translational modification, called carbonylation, irreversibly places a carbonyl group onto an amino acid residue, most commonly proline, lysine, arginine, and threonine. This modification can have severe consequences physiologically, including loss of solubility, loss of function, and protein aggregation.

Carbonylated proteins have commonly …

Photochemical Eilmination Reactions Via Zwitterionic Intermediates Generated By Electrocyclic Ring Closures, Majher Ibna Mannan Sarker

Dissertations (1934 -)

The research focuses on the design of photoremovable protecting groups that can be used to deprotect biological substrates of an organic compound by photolysis. The deprotection of the protecting group via photolysis requires heterolysis of a bond to the substrate. Heterolysis of a C-O or C-S σ-bonds in a zwitterionic intermediate is proposed. The photochemical electrocyclic reactions studied involve acrylanilides, benzothiophene carboxanilides, and N-(9-oxothioxanthenyl) benzothiophene carboxamides. α,β-Unsaturated anilides bearing leaving groups at the allylic position of the α-methylacrylamide group undergo photochemical electrocyclic ring closure with release of leaving group which could occur directly from a photochemically produced zwitterionic intermediate or …

Method For Arsenic Detection In Mine Samples From The Upper Peninsula Of Michigan, Vinay Babu Yalamanchili

All Capstone Projects

Arsenic is the 20th abundant element in the earth crust. High concentrations of Arsenic is seen in mine operating countries which can affect public health and biological environment. This may reach to drinking water through ground or surface run-off water. Long term exposure to arsenic causes cancer of bladder, skin, and lungs. So detecting the amount of arsenic in soil and drinking has been an analytical challenge. Arsenic is found in variety of chemical forms in organic and inorganic compounds which results in chemical and physical interferences in the analysis. Graphite Furnace Atomic Absorption Spectroscopy (GFAAS) was used to measure …

Literature Search On Using Dendrimer Nanoparticles As Drug Delivery Vehicles, Sivateja Kasaraneni

All Capstone Projects

The architectural design of dendrimers, multivalency, well-defined molecular weight and higher degree of branching differentiates them as unique and excellent nanocarriers in therapeutic applications such as drug delivery, gene transfection, tumor therapy, imaging and diagnostics. Nanoparticle drug-delivery systems are well known to increase the stability and selectivity of therapeutic agents. However immunogenicity, reticuloendothelial system uptake, drug leakage, cytotoxicity, hemolytic toxicity, poor aqueous solubility restrict the use of these drug delivery systems. These defects are overcame by surface engineering of the dendrimer molecule.

Drug molecule can be efficiently conjugated or encapsulated into the interior of the dendrimer or physically adsorbed onto …

Synthesis Of Half-Loaded Nitroimidazole Indocyanine Green Dyes Attached To Carbon Nanotubes, Courtney L. Stanford

Master's Theses

Indocyanine green dye is the only FDA approved NIR fluorescent dye that can be used in humans. 2-Nitroimidazoles are very effective radiosensitizers, have low cytotoxicity, and target hypoxic tissue. By coupling the two together, hypoxic tumors can be targeted and imaged. Previous work has been done to couple 2-nitroimidazole to both sides of the indocyanine green dye. This work focuses on expanding that concept to couple 2-nitroimidazole to only one side of the dye, thus allowing for the other end to be available to couple to another compound, generating a half loaded 2-nitroimidazole indocyanine green dye. In theory, this half-loaded …

Electrochemical Study Of Protein Modification, Jing Zhao, Xiao-Li Zhu, Gen-Xi Li

Journal of Electrochemistry

Protein post-translational modification is a key physiological procedure, which has received more and more research interests from the scientists not only in protein science but also in some other fields. The usually employed techniques for the study of protein modification include mass spectrum, affinity chromatography, etc. Considering the complexity of protein modification and the urgent demand of such kind of study, it is highly required to develop new techniques to perform more studies. Electrochemical methods, which have been widely used in chemical study and analysis, are playing an increasingly important role in many fields of biological studies. The modification of …

Hydrophilic Polymers Of Poly (2-Hydroxy Ethyl Methacrylate) With Tunable Properties For Drug Release, Sequestration Of Blistering Agent, Preparation Of Ultra-Strong Hydrogels & Thermal Stability Of Various Organic Azides, Ramakanth Ananthoji

USF Tampa Graduate Theses and Dissertations

The design and synthesis of new finely tunable porous materials has spurred interest in developing novel uses in a variety of systems. Zeolites, inorganic materials with high thermal and mechanical stability, in particular, have been widely examined for use in applications such as catalysis, ion exchange and separation. A relatively new class of inorganic-organic hybrid materials known as metal-organic frameworks (MOFs) has recently surfaced, and many have exhibited their efficiency in potential applications such as ion exchange and drug delivery. A more recent development is the design and synthesis of a subclass of MOFs based on zeolite topologies (i.e. ZMOFs), …

Synthesis And Cellular Investigations Of The 131-Lysyl Derivative Of Chlorin E6, Stewart Wynn Humble

Honors Capstones

No abstract provided.

Synthesis, Characterisation, And Preliminary In Vitro Studies Of Vanadium(Iv) Complexes With A Schiff Base And Thiosemicarbazones As Mixed Ligands, Nerissa A. Lewis, Fange Liu, Luke Seymour, Anthony Magnusen, Travis R. Erves, Jessa Faye Arca, Floyd A. Beckford, Ramaiyer Venkatraman, Antonio González-Sarrías, Frank R. Fronczek, Don G. Vanderveer, Navindra P. Seeram, Aimin Liu, William L. Jarrett, Alvin A. Holder

Faculty Publications

[VO(sal‐L‐tryp)(H₂O)] (1, sal‐L‐tryp = N‐salicylidene‐L‐tryptophanate) was used as a precursor to produce the new complexes [VO(sal‐L‐tryp)(MeATSC)]·1.5C₂H₅OH [2, MeATSC = 9‐Anthraldehyde‐N(4)‐methylthiosemicarbazone], [VO(sal‐L‐tryp)(N‐ethhymethohcarbthio)]·H₂O [3, N‐ethhymethohcarbthio = (E)‐N‐ethyl‐2‐(4‐hydroxy‐3‐methoxybenzylidene)hydrazinecarbothioamide] and [VO(sal‐L‐tryp)(acetylethTSC)]·C₂H₅OH {4, acetylethTSC = (E)‐N‐ethyl‐2‐[1‐(thiazol‐2‐yl)ethylidene]hydrazinecarbothioamide} by reaction with the respective thiosemicarbazone. The chemical and structural properties of these ligands and complexes were characterised by elemental analysis, ESI‐MS, FTIR, UV/Vis, ESR and ¹H and …

The Structural Requirements Of Histone Deacetylase (Hdac) Inhibitors: Suberoylanilide Hydroxamic Acid (Saha) Analogues Modified At C3, C6, And C7 Positions Enhance Selectivity, Sun Ea Choi

Wayne State University Dissertations

Histone deacetylase (HDAC) proteins are targets for drug design towards the treatment of cancers since overexpression of HDAC is linked to cancer. Several HDAC inhibitors, including the FDA approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat), have cleared clinical trials and emerged as anti-cancer drugs. However, SAHA inhibits all of the 11 metal ion-dependent HDAC proteins. Therefore, we synthesized several libraries of small molecule HDAC inhibitors based on SAHA to help understand the structural requirements of inhibitory potency and isoform selectivity.

In previous work, SAHA analogues functionalized at the C2 position (C2-SAHA analogues) near the metal binding hydroxamic acid displayed decreased …

Design, Synthesis, And Biological Evaluation Of Indole-Based 1,4-Disubstituted Piperazines As Cytotoxic Agents, Meri̇ç Köksal Akkoç, Mi̇ne Yarim Yüksel, İrem Durmaz, Rengül Çeti̇n Atalay

Turkish Journal of Chemistry

A series of 3-[(4-substitutedpiperazin-1-yl)methyl]-1H-indole derivatives were synthesized, and their structures were confirmed by spectral analysis. All the compounds were tested for their cytotoxic activity in vitro against 3 human tumor cell lines: human liver (HUH7), breast (MCF7), and colon (HCT116). Among the designed derivatives, most of the compounds showed significant cytotoxicity against liver and colon cancer cell lines with lower IC_{50} concentrations than the standard drug 5-fluorouracil. Compound 3s, with 3,4-dichlorophenyl substituent on the piperazine ring, was the most active in suppressing the growth of all screened cancer cells.

Design, Synthesis, And Biological Evaluation Of Novel Polyamine Transport System Probes And Their Application To Human Cancers, Aaron Muth

Electronic Theses and Dissertations

The mammalian polyamine transport system (PTS) has been of interest due to its roles in cancer and maintaining cellular homeostasis. Polyamines are essential growth factors which are tightly controlled via a balance of biosynthesis, metabolism, import, and export. This work focused on the development and biological testing of polyamine transport probes to help understand the molecular requirements of the PTS. This was mediated through the use of a CHO (PTS active) and CHO-MG* (PTS deficient) screen, where compounds demonstrating high toxicity in CHO and low toxicity in CHO-MG* were considered PTS selective. The first chapter focused on the development of …

Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang

Legacy Theses & Dissertations (2009 - 2024)

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various …

Syntheses And Characterization Of Water-Soluble Phythalocyanines For Diagnosis And Treatment Of Cancer, Benson Getenga Ongarora

LSU Doctoral Dissertations

Ongarora, Benson Getenga, B.S., Moi University, 2005 Doctor of Philosophy, Fall Commencement, 2012 Major: Chemistry Syntheses and Characterization of Water-Soluble Phthalocyanines for Diagnosis and Treatment of Cancer Dissertation directed by Professor M.Graҫa H. Vicente Pages in dissertation, xi. Words in abstract, 251. ABSTRACT Chapter 1 describes the general properties of phthalocyanines, synthesis of metallo-phthalocyanines, their photophysical features and their uses. The concepts of PDT and targeted therapeutics are also introduced. Chapter 2 describes the syntheses, characterization, photophysical studies and biological evaluation of cationic phthalocyanines. The trimethylaminophenoxy substituted phthalocyanines were synthesized through statistical condensation method, which gave a statistical mixture of …

Synthesis, Cellular Studies, And Computational Analysis Of Porphyrin And Bodipy Conjugates With Affinity For Epidermal Growth Factor Receptor, Alecia Michelle Mccall

LSU Doctoral Dissertations

Chapter 1 is a description of the basic fundamental concepts of porphyrins and BODIPYs, (including synthetic methodologies), a general mechanism of the processes of EGFR, and computational concepts that are elaborated upon in future chapters. Chapter 2 is a discussion solely on the porphyrins that were synthesized to be used as fluorophores for EGFR-targeted conjugates, both peptidic and non-peptidic. The porphyrins were primarily synthesized via the Lindsey method as well as by O-alkylation of tetrahydroxy porphyrins. Synthesis of PEG linkages are discussed as well through three methodologies. Chapter 3 is a presentation of the synthesis, characterization, cellular studies, and computational …

Total Synthesis Of A Virotoxin And Analogs For Conformational Studies, Benson Jumba Edagwa

LSU Doctoral Dissertations

This dissertation describes the first total synthesis of alloviroidin in trace amounts, along with that of three analogs containing L-proline (Pro), trans-3-hydroxyproline (3-Hyp) or cis-4-hydroxyproline (4-hyp) residue substituting for 2,3-trans-3,4-trans-dihydroxyproline in the natural product. We report herein an efficient strategy that provides a dipeptide containing a (2S,4S)-4,5-dihydroxyleucine (dihyLeu) residue, including a diastereoselective dihydroxylation. Nα-Carbobenzyloxy-(2S)-4,5-dehydroleucine was coupled with valine ethyl ester to give a dipeptide that was subjected to a Sharpless asymmetric dihydroxylation to introduce the diol. The relative configuration at C4 was assigned as S by X-ray crystallography after derivatization as an α-amino-γ-lactone hydrochloride salt. The preparation of the 2-(methylsulfonyl)tryptophan …

Single-Molecule Detection Of Molecular Beacons Generated From Ldr On Thermoplastic Microfluidic Device For Bioanalysis, Zhiyong Peng

LSU Doctoral Dissertations

Current clinical techniques for nucleic acid detection and analysis often involve PCR, lacking adequate specificity or sensitivity to meet the stringent requirements in certain applications. This research aims to develop an innovative molecular assay and the associated hardware to rapidly signal the presence of certain targets using reporter sequence found in their genome without requiring PCR. This assay coupled the sensitivity of single-pair fluorescence resonance energy transfer (spFRET) with the specificity of ligase detection reaction (LDR) to provide near real-time readout of target biomarkers. Heightened concerns on potential bioterrorism threats, such as rapid dissemination of pathogenic bacteria or viruses into …