Biochemistry Commons^™

Progress Toward The Total Synthesis Of Lyconadin A, Yu Zhang

Theses and Dissertations

Lyconadin A is a pentacyclic Lycopodium alkaloid isolated from the club moss Lycopodium complanatum with antitumor properties. We have developed a novel 7-exo/6-exo acyl radical cascade cyclization as a method of making the bicyclo[5.4.0]undecane ring system of lyconadin A. The model products are trans-fused ring systems, while a cis-fused ring system is needed in lyconadin A. We have discovered a method to convert the trans-fused model cascade cyclization product into the desired cis isomer. Based on Donohoe's pyridone synthesis, we developed a method for the construction of 5-alkyl and 3,5-dialkyl-6-carbomethoxy-2-pyridones, the former of which …

Synthesis And Evaluation Of N6,5'-Bis-Ureido-5'-Amino-5'-Deoxyadenosine Derivatives: Novel Nucleosides With Antiproliferative And Protein Kinase Binding Activities, Marcelio Oliveira

Theses and Dissertations

A new series of N6,5'-bis-ureido-5'-amino-5'-deoxyadenosine derivatives was prepared and evaluated for anticancer activities using the NCI 60 panel of human cancers. Certain of the derivatives showed promising activities (low micromolar GI50's) against several of the representative cancers. These included cell lines from the following general cell types in the NCI 60: Leukemia, Breast, Central Nervous System, Non-Small Cell Lung, Ovarian, Prostate, Renal, and Colon cancers. Select compounds were also screened for their affinities for protein kinases. The synthesis of the compounds was straightforward and involved N6 acylation with arylisocyanates, preceded by activation and nucleophilic substitution of the 5'-position to give …

Pore Size Characterization Of Monolithic Capillary Columns Using Capillary Flow Porometry, Yan Fang

Theses and Dissertations

A simple capillary flow porometer (CFP) was assembled for pore structure characterization of monolithic capillary liquid chromatography columns based on ASTM standard F316-86. Determination of differential pressures and flow rates through dry and wet samples provided the necessary information to determine the through-pore throat diameter, bubble point pore diameter, mean flow pore diameter, and pore distribution. Unlike measurements in bulk using traditional techniques to provide indirect information about the pore properties of monolithic columns, monoliths can be characterized in their original chromatographic forms with this system. The performance of the new CFP was first evaluated by characterizing the pore size …

Gas Phase Chiral Recognition, Characterization Of Porous Polymer Monolith Nanospray Ionization, And The Negative Mode Crafti Method Using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, Nannan Fang

Theses and Dissertations

Our group has been studying chiral recognition in gas phase using mass spectrometry for more than 10 years. We are interested in gas phase studies of fundamental interactions because the gas phase avoids complications and masking effects that may arise upon solvation. Therefore, the results of gas phase experiments can be directly compared with those of high-level computational studies. In chapter 2, I studied the roles of hydrogen bonding and pi stacking in gas phase chiral recognition between aromatic crown molecules and aromatic amines. High affinity between host and guest doesn't necessarily result in better recognition. If the affinity is …

Total Synthesis Of (-)-Acutumine, Fang Li

Theses and Dissertations

Acutumine is a tetracyclic alkaloid isolated from the Asian vine Menispermum dauricum with selective T-cell cytotoxicity and antiamnestic properties. We have developed a total synthetic route to this congested alkaloid, during which we also found a novel, stereoselective radical-crossover reaction that combines an intramolecular radical conjugate addition with a subsequent enolate hydroxylation. Key features of this synthesis also include a reagent-controlled diastereoselective ketone allylation, an anionic oxy-Cope rearrangement to form a congested quaternary sterocenter, a pyridine-mediated selective ozonolysis, and a Lewis acid promoted Michael-type cyclization.

Development Of Biocompatible Polymer Monoliths For The Analysis Of Proteins And Peptides, Yun Li

Theses and Dissertations

Biocompatibility is an important issue for the development of chromatographic stationary phases for the analysis of biomolecules (including proteins and peptides). A biocompatible stationary phase material is a material that resists nonspecific adsorption of biomolecules and does not interact with them in a way that would alter or destroy their structures or biochemical functions. The monolithic column format is a good alternative to typical spherical particle packed columns for capillary liquid chromatography of biomacromolecules. Several novel anion-exchange polymer monoliths for the analysis of proteins were synthesized for improved biocompatibility. Two novel polymeric monoliths were prepared in a single step by …

Real-Time Virus Analysis Via Image Charge Detection Surface Induced Dissociation Tandem Mass Spectrometry, Seth T. Call

Theses and Dissertations

This thesis reports on the development of a novel mass spectrometer combining image charge detection with surface induced dissociation for real-time analysis of intact viruses. Protonated viruses produced using electrospray are accelerated and subsequently impact on a solid surface. Capsid peptides released during the impact are analyzed using time-of-flight mass spectrometry. Image charge detection is used to measure the mass and charge states of structurally intact, electrosprayed viruses prior to impact. Since virus capsids are composed of loosely-bound proteins, collision of viruses with surfaces at moderate impact energies could release intact proteins. The masses and numbers of different protein types …

Design And Characterization Of A Human Exposure Chamber And Inversion Episodes In Salt Lake City, Utah In January/February Of 2009, Roman Yuri Kuprov

Theses and Dissertations

Research on health effects of particulate matter (PM) has been a very active area in the last two decades. One plausible mechanism by which exposure to PM affects human health includes modification of autonomic endothelium function. Decreased endothelium activity causes heightened risks of cardiovascular disease. A human exposure chamber designed to conduct experiments to quantify diminished function of endothelium from short term exposure to PM is described. The chamber consists of two stages for containment and pre-treatment of PM and exposure of human subjects. Concentrations of CO, CO2, NO, NO2, O3, and PM2.5, are monitored and controlled in the exposure …

A Top-Down Proteomic Approach For The Discovery Of Novel Serum Biomarkers Of Pregnancy-Related Disease, Karen Merrell

Theses and Dissertations

The serum fraction of blood is an ideal material in which to search for novel biomarkers for disease. It is easily obtained through relatively non-invasive means, routinely collected, and a rich treasure-trove of information about the health of an individual. Cells react to signal molecules, take up nutrients, and release waste products, fragments that are the result of proteolysis, and other molecules out into the bloodstream. If these components are unique to the cells in question, that part of the complex mixture that is the blood stream can potentially characterize the health of the tissue or organ those cells are …

Ion Transport Behaviors Upstream And Downstream From The Sampling Cone Of An Inductively Coupled Plasma Mass Spectrometer, Haibin Ma

Theses and Dissertations

Inductively coupled plasma - mass spectrometry (ICP-MS) is the technique of choice worldwide for trace elemental determinations because of its excellent ionization ability, low detection limits and fast analysis speeds. However, the ICP-MS still suffers from some disadvantages, such as spectral overlap and severe matrix effects. Matrix effects or interferences, partly arise from changes in the analyte transmission through the interfacial region between the ICP and mass spectrometer with changes in sample matrix. Better understanding of the transmission behaviors of analyte through the sampling and skimmer cones will provide the insights needed to alleviate matrix interferences and to improve the …

Relaxation Of Vibrationally Excited Trifluorobenzene And Tetrafluorobenzene By Collisions With Carbon Dioxide, Alan M. Johnson

Theses and Dissertations

An investigation into the relaxation of highly vibrationally excited trifluorobenzene and tetrafluorobenzene following collisions with carbon dioxide was performed using diode laser transient absorption spectroscopy. A 248 nm excimer laser prepared the vibrationally hot (E'~41,000 cm-1) fluorobenzene molecules. Large amounts of translational and rotational energy are transferred through collisions between the hot donor molecule and CO2. Rate constants and collisional probabilities were calculated by probing the high J states (J=58~80) of CO2 in the vibrational ground state, 0000, with measurements taken 1 µsec, ¼ the mean gas collision time, following each excimer laser pulse. The energy transfer probability distribution function, …

The Role Of Smpb In The Early Stages Of Trans-Translation, Deanna June Cazier

Theses and Dissertations

Ribosomes stall on defective messenger RNA transcripts in eubacteria. Without a mechanism to release stalled ribosomes, these cells would die. Transfer-messenger RNA (tmRNA) and small protein B (SmpB) reactivate stalled ribosomes in a process known as trans-translation. Together, tmRNA and SmpB mimic alanyl-tRNA, entering the A site of stalled ribosomes and accepting transfer of the stalled polypeptide. A portion of tmRNA is then positioned as a template for the ribosome to resume translating. The tmRNA open reading frame encodes a proteolysis tag to mark the aberrant polypeptide for degradation and a stop codon to release the ribosome. How are tmRNA …

Novel Cinchona Alkoloid Derived Ammonium Salts As Phase-Transfer Catalysts For The Asymmetric Synthesis Of Beta-Hydroxy Alpha-Amino Acids Via Aldol Reactions And Total Synthesis Of Celogentin C., Bing Ma

Theses and Dissertations

Project I. Cinchona alkaloid-derived quaternary ammonium salts have been successfully used as phase-transfer catalysts, particularly in asymmetric alkylations. Our group applied this type of catalyst in the synthesis of β-hydroxy α-amino acids via aldol reactions and discovered that the Park-Jew catalyst afforded good yields and good enantiomeric excess of the syn diasteromers, but negligible diastereoselectivity. This project was therefore focused on the synthesis of novel cinchonidine-derived catalysts with the Park-Jew catalyst as the lead structure. The C3 position of cinchonidine nucleus was modified to achieve dimers and catalysts possessing electron-deficient alkyne and alkene moieties. Synthesized catalysts were tested in the …

Mnte-2-Pyp And Radiation In A Prostate Cancer Model: Implications For Radiotherapy, Adeola Y. Makinde

Loma Linda University Electronic Theses, Dissertations & Projects

A major limitation of successful radiation therapy in cancer treatment is the increase in normal tissue damage as higher doses are used to achieve greater tumor destruction. Radiation dose optimization in cancer therapy requires achieving maximum tumor destruction with minimal damage to normal tissue Antioxidants have been shown to protect normal tissues against radiation damage, as radiation-induced tissue damage results predominantly from reactive oxygen species that directly damage cellular components. However, for effective use as normal tissue radioprotectants in radiotherapy, these antioxidants must not protect the tumors. Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) is a metalloporphyrin antioxidant that has been …

Genetic Analysis Of Ribosome Stalling And Rescue, Douglas Ray Tanner

Theses and Dissertations

In eubacteria, ribosome stalling on broken messenger RNA transcripts can lead to cell death. The trans-translation quality control mechanism rescues many of these stalled ribosomes. In this process, tmRNA enters stalled ribosomes by mimicking a transfer RNA, accepting the stalled nascent peptide. The ribosome then releases the broken mRNA and resumes translation on a coding region within tmRNA itself. Translation of tmRNA marks the nascent peptide for destruction by the addition of a short proteolysis tag and the ribosome is released at a stop codon within the tmRNA open reading frame. An intriguing aspect of trans-translation is that …

Synthesis And Evaluation Of Stimulatory Properties Of Glycolipids For Natural Killer T Cells, Xiangtian Long

Theses and Dissertations

Natural killer T cells (NKT cells) are a subset of T cells. They regulate a wide range of diseases including infection, tumor growth, and autoimmune diseases, through recognizing glycolipid antigens in the context of CD1d. An understanding of the scope of glycolipid antigens would facilitate use of this cell type in controlling immune responses. Till today, a lysosomal glycolipid, isoglobotrihexosylceramide (iGb3), is the only natural glycolipid that has been found to be recognized by both human and mouse NKT cells. To elucidate the molecular basis of this specific recognition, iGb3 variants were designed and prepared: i) replacement of the C26 …

Engineering The Nanoparticle Surface For Protein Recognition And Applications, Mrinmoy De

Open Access Dissertations

Proteins and nanoparticles (NPs) provide a promising platform for supramolecular interaction. We are currently exploring both fundamental and applied aspects of this interaction. On the fundamental side, we have fabricated a series of water-soluble anionic and cationic NPs to interact with cationic and anionic proteins respectively. A Varity of studies such as, activity assay, fluorescence titration, isothermal titration calorimetry etc. were carried out to quantify the binding properties of these functional NPs with those proteins. Those studies reveal the prospect of tuning the affinity between the nanoparticles and proteins by the surface modification. On the application side, we have used …

A Comparative Study Of The Structural Features And Kinetic Properties Of The Mofe And Vfe Proteins From Azotobacter Vinelandii, Miguel Alejandro Pabon Sanclemente

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Biological nitrogen fixation is accomplished in the bacterium Azotobacter vinelandii by means of three metalloenzymes: The molybdenum, vanadium, and iron-only nitrogenase. The knowledge regarding biological nitrogen fixation has come from studies on the Mo-dependent reaction. However, the V- and Fe-only-dependent reduction of nitrogen remains largely unknown.

By using homology modeling techniques, the protein folds that contain the metal cluster active sites for the V- and Fe-only nitrogenases were constructed. The models uncovered similarities and differences existing among the nitrogenases regarding the identity of the amino acid residues lining pivotal structural features for the correct functioning of the proteins. These differences, …

Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cisplatin is a common therapeutic agent used in cancer treatment. Unfortunately, resistance to cisplatin in addition to severe side effects limits its use in cancer treatment. Two novel cisplatin analogues, 4DB and 4TB were shown to have varying cytotoxicity in lung, breast and prostate cancer cells. The hypothesis for this study states that the differences in 4DB and 4TB cytotoxicity among different tissue types is due to the type and efficiency of DNA repair mechanisms involved in response to these drugs.

To test the hypothesis, proteins involved in the rate limiting step of nucleotide excision repair (NER) and mismatch repair …

Synthesis Of 2,4,5-Triaminocyclohexane Carboxylic Acid As A Novel 2-Deoxystreptamine Mimetic, Sarah Elizabeth Roberts

Theses and Dissertations

RNAs have become increasingly recognized as possible drug targets due to their involvement in important biochemical functions, as well as their unique but well-defined structures. Recently published crystal structures depict the binding of a series of aminoglycosides- or more specifically- 2-deoxystretamine (2-DOS), the most preserved central scaffold of aminoglycosides, to a conserved 5'-GU-3'region on their target RNAs. A novel unnatural γ-amino acid, 1, has been synthesized using 2-deoxystreptamine as a template through structure-based rational design. The unnatural amino acid has been designed to replace a glycosidic linkage with an amide bond, which may limit the promiscuous binding characteristics of aminoglycosides …

Role Of Molecular Chaperones In G Protein B5-Regulator Of G Protein Signaling Dimer Assembly And G Protein By Dimer Specificity, Alyson Cerny Howlett

Theses and Dissertations

In order for G protein signaling to occur, the G protein heterotrimer must be assembled from its nascent polypeptides. The most difficult step in this process is the formation of the Gβγ dimer from the free subunits since both are unstable in the absence of the other. Recent studies have shown that phosducin-like protein (PhLP1) works as a co-chaperone with the cytosolic chaperonin complex (CCT) to fold Gβ and mediate its interaction with Gγ. However, these studies did not address questions concerning the scope of PhLP1 and CCT-mediated Gβγ assembly, which are important questions given that there are four Gβs …

Functionalization, Characterization, And Applications Of Diamond Particles, Modification Of Planar Silicon, And Chemoetrics Analysis Of Ms Data, Li Yang

Theses and Dissertations

In spite of the stablility (lack of reactivity) of diamond powder, I have developed a method for tethering alkyl chains and polymers to deuterium/hydrogen-terminated diamond. One method is through ether linkages via thermolysis of di-tert-amyl peroxide (DTAP). This reaction with DTAP has also been applied to grow polymers on the diamond surface. The other method is atom transfer radical polymerization (ATRP), which was applied to grow polystyrene at the surface of diamond. Both polystyrene-modified diamond and sulfonated polystyrene-modified diamond can be prepared by either method, and can be used for solid phase extraction. Diamond stationary phases are stable under basic …

The First Attachment And Post-Functionalization Of Polybutadiene And Thio-Click Functionalized Polybutadiene On H-Terminated Si(111), Todd Devere Wickard

Theses and Dissertations

I report the attachment of polymers with pendant vinyl groups to hydrogen-terminated silicon(111) (Si(111)-H) under mild conditions. 1,2-addition polybutadiene (Mw 3200-3500) was attached to Si(111)-H at room temperature with visible light. I also report the partial functionalization, in solution, of 1,2-addition polybutadiene with various thiols using thiol-click chemistry. These compounds bind to Si(111)-H via visible light activation. The partially functionalized polybutadienes allow further functionalization at the surface through unreacted carbon-carbon double bonds. Surfaces were characterized with contact angle goniometry, spectroscopic ellipsometry, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and atomic force microscopy (AFM).

Polymer Microfluidic Devices For Bioanalysis, Xuefei Sun

Theses and Dissertations

Polymeric microchips have received increasing attention in chemical analysis because polymers have attractive properties, such as low cost, ease of fabrication, biocompatibility and high flexibility. However, commercial polymers usually exhibit analyte adsorption on their surfaces, which can interfere with microfluidic transport in, for example, chemical separations such as chromatography or electrophoresis. Usually, surface modification is required to eliminate this problem. To perform stable and durable surface modification, a new polymer, poly(methyl methacrylate-co-glycidyl methacrylate) (PGMAMMA) was prepared for microchip fabrication, which provides epoxy groups on the surface. Whole surface atom transfer radical polymerization (ATRP) and in-channel ATRP approaches were employed to …

Vibrational Spectroscopy Of Isotopically Labeled Indoles And Electron Transfer Involving Indole (Tryptophan) Radicals, Senghane Dominique Dieng

Theses, Dissertations and Culminating Projects

Vibrational spectroscopy of tryptophan can be used as a probe for local protein conformation and to study protein electron transfer. For the interpretation of the vibrational spectra, the proper assignment of the vibrational bands to normal modes is essential. We report the experimentally measured infrared and Raman spectra of tryptophan, indole and 3-methylindole as well as of several of their isotope substituted forms; tryptophan indole-d₅ and -¹⁵N₂, and indole 2-¹³C. The effect of the exchange of the indole NH to ND on the vibrational spectra of these molecules was also determined. The measurements …

Genetically Engineered Repetitive Polypeptides : Design, Synthesis, Characterization, And Applications, Natalya I. Topilina

Legacy Theses & Dissertations (2009 - 2024)

This work is dedicated to the investigation of protein folding with the emphasis on the aggregation and amyloid fibrils formation. The focus of the research is to elucidate the relationship between polypeptide chain sequence and folding/aggregation properties. For this purpose, i) libraries of the de novo macromolecular repetitive β-sheet forming polypeptides were designed, and ii) the strategy for their rapid creation was developed. The strategy enables retention of a basic polypeptide core, yet allowing variations in the repetitive sequence, degree of polymerization and distribution of specific amino acids. The polypeptides were expressed in E. coli, purified, and characterized by various …

Asymmetric Transfer Hydrogenation Of Allylic Alcohols With Homogeneous Chiral Ruthenium Catalysts: A Proposed Mechanism, Marie G. Beauchamps

Seton Hall University Dissertations and Theses (ETDs)

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Identification And Quantification Of Polycyclic Musks And Methyl-Triclosan In Unknown Freshwater Fish Tissue Samples, Elizabeth Mara Jacobs

Dissertations, Theses, and Masters Projects

No abstract provided.