Digital Commons Network^™

The Role Of Upstream Sequences In Selecting The Reading Frame On Tmrna, Allen R. Buskirk, Mickey R. Miller, David W. Healey, Jonathan D. Dewey, Stephen G. Robison

Faculty Publications

tmRNA acts first as a tRNA and then as an mRNA to rescue stalled ribosomes in eubacteria. Two unanswered questions about tmRNA function remain: how does tmRNA, lacking an anticodon, bypass the decoding machinery and enter the ribosome? Secondly, how does the ribosome choose the proper codon to resume translation on tmRNA? According to the -1 triplet hypothesis, the answer to both questions lies in the unique properties of the three nucleotides upstream of the first tmRNA codon. These nucleotides assume an A-form conformation that mimics the codon-anticodon interaction, leading to recognition by the decoding center and choice of the …

Quantitative Measure Of Cytotoxicity Of Anticancer Drugs And Other Agents., Zhimin Tao, Eyone Jones, Jerry Goodisman, Abdul-Kader Souid

Chemistry - All Scholarship

Many anticancer drugs act on cancer cells to promote apoptosis, which includes impairment of cellular respiration (mitochondrial O(2) consumption). Other agents also inhibit cellular respiration, sometimes irreversibly. To investigate the sensitivity of cancer cells to cytotoxins, including anticancer drugs, we compare the profiles of cellular O(2) consumption in the absence and presence of these agents. Oxygen measurements are made at 37 degrees C, using glucose as a substrate, with [O(2)] obtained from the phosphorescence decay rate of a palladium phosphor. The rate of respiration k is defined as -d[O(2)]/dt in a sealed container. Different toxins produce different profiles of impaired …

Working Report On The Status Quo Of Nanomaterials Impact On Health And Environment, Harald Krug, Margarita Apostolova, Marite Arija Bake, Gordon Chambers, Horia Chiriac, Eva Herzog, Victoria Hand, Jürgen Höck, Peter Hoet, Nicoleta Lupu, Declan Mccormack, Maja Remskar, George Robillard, Jamila Smisterova, Jan Stetkiewicz, Speranta Tanasescu, Aris Tsatsakis, David Vaughn, Peter Wick, Jörg Wörle-Knirsch

Articles

Nanotechnology is regarded as one of the key technologies of the future and associated with high expectations by politics, science and economy. Artificially produced nanosized particles and nanoscale system components have new properties which are of importance for the development of new products and applications. Such new properties of materials and substances result from the special properties of surfaces and interfaces and in part, from the geometric shape of the material. In theory nanoparticles (NPs) can be produced from nearly any chemical; however, most NPs that are currently in use today have been made from transition metals, silicon, carbon (single-walled …

Development And Investigation Of Unique Organic Materials To Detect Disease Biomarkers, George Kiplimo Samoei

Dissertations and Theses

Chemomechanical polymer gels with the capability of recognizing specific biological molecules are promising materials for many biomedical applications. Glucose-selective hydrogels have potential utility in the continuous monitoring of glucose and glucose-triggered insulin delivery for the management of diabetes. Herein, the development and study of the first material which detects glucose via significant volume changes in the challenging matrix human blood plasma is described. The material was created via the modification of PMMA with supramolecular binding sites. The polymer exhibits excellent selectivity and reversibility including continuous expansion-contraction cycles.

The Role Of The Tight-Turn, Broken Hydrogen Bonding, Glu222 And Arg96 In The Post-Translational Green Fluorescent Protein Chromophore Formation, Marc Zimmer, Nathan P. Lemay, Alicia L. Morgan, Elizabeth J. Archer, Luisa A. Dickson, Colleen M. Megley

Chemistry Faculty Publications

Green fluorescent proteins (GFP) and GFP-like proteins all undergo an autocatalytic post-translational modification to form a centrally located chromophore. Structural analyses of all the GFP and GFP-like proteins in the protein databank were undertaken to determine the role of the tight-turn, broken hydrogen bonding, Gly67, Glu222 and Arg96 in the biosynthesis of the imidazolone group from 65SYG67. The analysis was supplemented by computational generation of the conformation adopted by uncyclized wild-type GFP. The data analysis suggests that Arg96 interacts with the Tyr66 carbonyl, stabilizing the reduced enolate intermediate that is required for cyclization; the carboxylate of Glu222 acts as a …

Origin Of The Absorption Maxima Of The Photoactive Yellow Protein Resolved Via Ab Initio Multiconfigurational Methods, Pedro B. Coto, Sergio Martí, Monica Oliva, Massimo Olivucci, Manuela Merchan, Juan Andre

Chemistry Faculty Publications

We discuss the role of the protein in controlling the absorption spectra of photoactive yellow protein (PYP), the archetype xanthopsin photoreceptor, using quantum mechanics/molecular mechanics (QM/MM) methods based on ab initio multireference perturbation theory, combined with molecular dynamics (MD) simulations. It is shown that in order to get results in agreement with the experimental data, it is necessary to use a model that allows for a proper relaxation of the whole system and treats the states involved in the electronic spectrum in a balanced way, avoiding biased results due to the effect of nonrepresentative electrostatic interactions on the chromophore.

Photoactive Supramolecular Cyclodextrin Assemblies, Muath Atmeh

Doctoral

Ligands with a macrocyclic host unit attached to a photoactive metal core are of interest across a range of applications from luminescent or electrochemical sensors, light harvesting and energy-collection purposes. Their versatile properties and possibility of associating cyclodextrins with other molecules both covalently and non-covalently mean that these macrocyclic ligands can be employed in the design and the formation of supramolecular complexes. A particularly attractive proposition is to combine the selective inclusion capabilities of CD with luminophores which may act as reporters of binding or other interactions at the cyclodextrin cavity. Ruthenium, osmium, and iridium polypyridyl complexes are particularly attractive …

Exploration Of The Chemical And Biological Processes Through Molecular Dynamics Simulation And Blocklocalized Wavefunction Method, Yuchun Lin

Dissertations

Computer simulation plays a crucial role in interpreting, unifying and guiding experimental observations. In this dissertation, molecular dynamics (MD) simulations and the block-localized wavefunction (BLW) method have been used to explore the chemical and biological processes.

Detailed MD simulations were performed to study the transportation of NH₄⁺, NH₃ and H₂O through the Escherichia coli ammonium transporter (AmtB) membrane protein. A periplasmic recruitment vestibule was identified and the entrance of an NH₄⁺ into this vestibule requires only 3.1 kcal/mol. In the end of this vestibule, the phenyl ring of Phe107 dynamically opens and …

Probing The Effects Of Heterogeneity On Delocalized Π⋯Π Interaction Energies, Desiree M. Bates, Julie A. Anderson, Ponmile Oloyede, Gregory S. Tschumper

Chemistry Faculty Research & Creative Works

Dimers composed of benzene (Bz), 1,3,5-triazine (Tz), cyanogen (Cy) and diacetylene (Di) are used to examine the effects of heterogeneity at the molecular level and at the cluster level on π⋯π stacking energies. The MP2 complete basis set (CBS) limits for the interaction energies (E int) of these model systems were determined with extrapolation techniques designed for correlation consistent basis sets. CCSD(T) calculations were used to correct for higher-order correlation effects (δECCSD(T)MP2) which were as large as +2.81 kcal mol^-1. The introduction of nitrogen atoms into the parallel-slipped dimers of the aforementioned molecules causes significant changes to E …

A Set Of Phosphatase-Inert “Molecular Rulers” To Probe For Bivalent Mannose 6-Phosphate Ligand-Receptor Interactions, Xiang Fei, Christopher M. Connelly, Richard G. Macdonald, David B. Berkowitz

David Berkowitz Publications

A set of bivalent mannose 6-phosphonate “molecular rulers” has been synthesized to examine ligand binding to the M6P/IGF2R. The set is estimated to span a P-P distance range of 16–26 Å (MMFF energy minimization on the hydrated phosphonates). Key synthetic transformations include sugar triflate displacement for phosphonate installation and Grubbs I cross-metathesis to achieve bivalency. Relative binding affinities were tested by radioligand displacement assays versus PMP-BSA (pentamannose phosphate-bovine serum albumin). These compounds exhibit slightly higher binding affinities for the receptor (IC_50’s = 3.7–5 μM) than the parent, monomeric mannose 6-phosphonate ligand and M6P itself (IC₅₀ = 11.5 ± …

Synthesis Of Substituted 2-Amino-Cyclobutanones, Nicola Armoush, Preeti Syal, Daniel P. Becker

Chemistry: Faculty Publications and Other Works

A series of weakly nucleophilic nitrogen derivatives including carbamates, amides, sulfonamides, and anilines were reacted with 1,2‐bis(trimethylsilyloxy)cyclobutene under acidic conditions to afford various substituted 2‐aminocyclobutanone derivatives 3a–i in modest to excellent yields.

Correlation Between Luminescent Properties And Local Coordination Environment For Erbium Dopant In Yttrium Oxide Nanotubes, Yuanbing Mao, John Bargar, Michael Toney, Jane P. Chang

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

The local dopant coordination environment and its effect on the photoluminescent (PL) spectral features of erbium-doped yttrium oxide nanotubes (NTs) were probed by synchrotron-based x-ray diffraction (XRD), x-ray absorption near-edge spectroscopy (XANES), and extended x-ray absorption fine structure (EXAFS). XRD, XANES, and EXAFS data demonstrate that single phase solid solutions of Y (2-x) Erx O3 were formed at 0≤x

Characterization Of Commercial Pectin Preparations By Spectroscopic And Chromatographic Techniques., Daniel Wayne Dixon

Electronic Theses and Dissertations

Pectin has a long history as a food additive. However, elucidation of its fine structural and property relationships remains elusive. Recent research has focused on pectin's ability to complex with divalent heavy metals to aid in characterizing it. Commercial pectins of unknown composition were obtained from local grocers. Purified pectin samples from orange peel, lemon peel, and apple pomace, each of low and high levels of methyl esterification and of unknown distribution pattern were also purchased. Instead of metal complexation, several highly absorbing dyes such as Ruthenium Red, Nile Blue, and Acridine Orange were used to complex with the pectins …

Identification Of Guanylate Cyclases And Related Signaling Proteins In Sperm Tail From Sea Stars By Mass Spectrometry, Mia Nakachi, Midori Matsumoto, Philip M. Terry, Ronald L. Cerny, Hideaki Moriyama

Hideaki Moriyama Publications

Marine invertebrates employ external fertilization to take the advantages of sexual reproduction as one of excellent survival strategies. To prevent mismatching, successful fertilization can be made only after going though strictly defined steps in the fertilization. In sea stars, the fertilization process starts with the chemotaxis of sperm followed by hyperactivation of sperm upon arriving onto the egg coat, and then sperm penetrate to the egg coat before achieving the fusion. To investigate whether the initiation of chemotaxis and the following signaling has species specificity, we conducted comparative studies in the protein level among sea stars, Asterias amurensis, A. forbesi …

Identification Of Metallo-Ss-Lactamase Inhibitors Via Enzyme Assay And Hplc-Ms Monitoring, Peggy Ann Sanchez

Theses, Dissertations and Culminating Projects

The vast overuse of antibiotics along with extrachromosomal gene insertion between different bacterial species has led to the Darwinian consequence of antibiotic resistance. Amongst the contributing factors to the rise of bacterial resistances are the production of ß-lactamases, which pose a major impediment to treatment with ß-lactam drugs such as penicillins and carbapenems. SPM-1 is a metallo-ß-lactamase (MBL) that confers antibiotic resistance to bacteria through zinc-mediated hydrolysis of ß-lactams. Bacteria that express the SPM-1 metalloenzyme show reduced sensitivity to ß-lactam drugs. One method to defeat this form of resistance is to administer a ß-lactam antibiotic with a potent ß-lactamase inhibitor …

Preparation And Characterization Of Macroporous Electrodes For Electrochemical Bioassays, Ashwin Rao

All Dissertations

Applications such as point-of-care medical diagnosis and in-the-field biological warfare agent detection require portable bioassays which are less laborious yet cost effective. Conventional sandwich bioassays see limited use for such applications as it involves time consuming steps of reagent treatment and washings, and are restricted to use inside laboratories. We explore new platforms for sandwich bioassays required by such applications. The platform we have developed is based on electrochemical methods of detection. Flow-through three-dimensional electrodes suitable for use in electrochemical sandwich bioassays were fabricated. A composite of superporous agarose and reticulated vitreous carbon (SPA-RVC) material was used for the fabrication …

Synthetic Studies And Biological Evaluation Of Imidazole-Containing Marine Alkaloids, Lesley Ann Schmid

Chemistry & Biochemistry Dissertations - Archive

This dissertation discusses the synthetic methods towards and the preliminary biological studies of an unnamed, imidazole-containing alkaloid, derived from the marine species Oceanapia. This alkaloid was first discovered in 1996 by researchers at the NIH as a possible inhibitor of the key enzyme in the detoxification cycle of Mycobacterium tuberculosis. Chapter 1 provides an overview of tuberculosis, which is currently the second highest cause of death worldwide, with one third of the world's population infected. In recent years, the emergence of multi-drug resistant strains has created new interest and funding for tuberculosis research. New treatments like the alkaloid described above …

Optimization Of Expression And Purification Of Acetoacetyl-Coa Thiolase From Sunflower, Anthony Muriithi Maina

Theses, Dissertations and Culminating Projects

The [beta]-oxidation system in sunflower (Helianthus annuus L.) cotyledons is distinguished by the existence of two different thiolase isoforms, Thiolase I (acetoacetyl-CoA thiolase, EC 2.3.1.9 AACT) and Thiolase II (3-oxoacyl-CoA thiolase, EC 2.3.1.16 OACT). Glyoxysomal AACT is the last enzyme in the p-oxidation of fatty acids in plant glyoxysomes. Glyoxysomal AACT has been successfully cloned, expressed and purified from sunflower cotyledons (Dyer et al., 2006). In this paper we investigate the optimal conditions for both expression and purification. These include the choice of vector, the growth conditions and the purification parameters for the maximum possible yield of AACT protein.

The Effects Of Physical And Chemical Modulating Agents On The Induction Of Vaccine-Induced Immune Responses, Andrea Nicole Ryan

Honors Scholar Theses

After the development of the viral-based prostate cancer vaccine, Ad5-PSA, much research has been orientated to help enhance the induced immune response by combining the vaccine with physical and chemical modulating agents, more specifically the polymers polyethylenimine (PEI), chitosan, and chitosan coated with CD3 complex antibodies; all previously shown to stimulate an immune response as isolated gene carriers. To compare the vaccine-induced immune responses between the naked vaccine and the polymer-vaccine combinations, a mouse model using the ovalbumin- specific Ad-OVA vaccine was tested using intracellular cytokine staining (ICS), tetramer staining, and cytotoxic T-cell lymphocyte assays to measure the activation of …

Synthesis And Characterization Of Polymeric Materials Derived From Multifunctional Alkyl A-Hydroxymethylacrylates, Jean-Francois Morizur

Dissertations

The research presented in this dissertation covers the investigation of new materials derived from alkyl a-hydroxymethylacrylates (RHMA). The first project exposed in Chapter II involves the synthesis, characterization of RHMA-based reactive surfactants and their successful incorporation in acrylic latexes. The amphiphilic monomers testify of a good copolymerization behavior with other acrylic monomers such as methyl methacrylate and butyl acrylate although their extensive bulkiness. They led to the formation of well-defined polymeric particles via a seeded emulsion polymerization process and permitted decreasing significantly the water sensitivity of the resulting films as compared to film incorporating conventional emulsifier such as sodium dodecyl …

Targeted Drug Delivery Systems For Cancer Therapy, Antonio Clementi, Christine O'Connor, Mary Mcnamara, A. Mazzaglia, M. C. Aversa, A. Giuffrida

Conference Papers

The role of cyclodextrin’s (CD) in drug delivery has advanced in recent years and this may be attributed to its biocompatibility and well established synthesis. Chemical modification of CDs has shown to extend the physicochemical properties and the host capacity for a variety of drugs. β-CD has been widely used in the early stages of pharmaceutical applications because of its ready availability and its cavity size suitability for a wide range of drugs. Chemical modification of β-CD has proven to enhance aqueous solubilisation, microbiological stability and reduced toxicity in previous studies.1 Folate Receptors are over-expressed in several human cancers including …

The Design, Synthesis, And Controlled Polymerization Of Cationic And Zwitterionic Norbornene Derivatives, David Allen Rankin

Dissertations

Ring-opening metathesis polymerization (ROMP) has been exploited for the controlled polymerization of cationic and zwitterionic norbornene-based monomers and employed in the preparation of homo- and block-copolymer systems in homogeneous organic media without the use of post-polymerization modification or protecting group chemistries. Relying on previous knowledge of certain halogenated alcoholic organic solvents capable of solubilizing hydrophilic monomers, the first study, describes the synthesis and controlled polymerization of a series of new permanently cationic ammonium exo-7- oxanorbornene derivatives M31 via ROMP, with the first generation Grubbs catalyst 17, in a novel solvent mixture comprised of 1:1 vol/vol 2,2,2-trifluoroethanol (TFE)/methylene chloride (CH2CI2). This …

Iron(Iii)-Salophene: An Organometallic Compound With Selective Cytotoxic And Anti-Proliferative Properties In Platinum-Resistant Ovarian Cancer Cells, Thilo S. Lange, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Carolyn Mccourt, Laurent Brard

Chemistry Faculty Publications and Presentations

Background: In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovariancancer cell lines were investigated.

Methodology/Principal Findings: Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 μM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed …

Carbon Nanotubes And Nanocomposites For Thermal And Electrical Applications, Wei Wang

All Dissertations

The known electrical and thermal properties of carbon nanotubes have prompted many predictions on their extraordinary potentials for ultimately performing polymeric nanocomposites. In this dissertation, chemical modification and functionalization of carbon nanotubes have been demonstrated as being effective for high-quality polymeric carbon nanotube composites, especially with our approach of using polymers that are structurally identical or maximally similar to the matrix polymers in the nanotube functionalization. For example, a poly(N-vinyl carbazole) (PVK) copolymer containing pendant hydroxyl groups was synthesized for the functionalization of single-walled carbon nanotubes (SWNTs). The shared solubility of the functionalized nanotube samples with PVK matrix polymer enabled …

A Comparison Of The Surface Adsorption Characteristics Of Reduced And Oxidized Cytochrome C On A Fused Silica Surface Via Attenuated Total Internal Reflection Spectroscopy, Casey M. Kraning

Undergraduate Honors Thesis Collection

No abstract provided.

Method Of Preparing A Chiral Substrate Surface By Electrodeposition, Jay A. Switzer, Hiten M. Kothari, Shuji Nakanishi, Eric W. Bohannan

Chemistry Faculty Research & Creative Works

A solid substrate comprising a surface comprising an achiral array of atoms having thereupon a chiral metal oxide surface. The chiral metal oxide surface is prepared by electrodeposition of a chiral metal oxide array from a solution of a chiral salt of the metal. In one embodiment, chiral CuO is grown on achiral Au(001) by epitaxial electrodeposition. The handedness of the film is determined by the specific enantiomer of tartrate ion in the deposition solution. (R,R)- tartrate produces an S—CuO(l 1 T) film, while (S,S)-tartrate produces an R—CuO(Tl 1) film. These chiral CuO films are enantiospecific for the electrochemical oxidation …

Mechanistic Studies On The Electrochemistry Of Glutathione And Homocysteine, Olufemi Oyesanya

Theses and Dissertations

This research work has investigated the electrochemistry of glutathione (GSH)and homocysteine (HCSH) in order to develop sensors for these biological thiols.Ru(bpy)₃³⁺ and IrCl₆²⁻ have been used as mediators for the electrooxidation of GSH andHCSH because direct oxidation of these thiols is slow at most conventional electrodes.The electrochemical detection of GSH and HCSH has been pursued because of their biological roles.

Concerted proton electron transfer (CPET) and stepwise proton electron transfer(PT/ET) pathways have been observed in the electrooxidation of GSH and HCSH.Oxidation of GSH by Ru(bpy)₃³⁺ carried out in deuterated and undeuterated buffered (pH= pD …

Co2 Fixation Kinetics Of Halothiobacillus Neapolitanus Mutant Carboxysomes Lacking Carbonic Anhydrase Suggest The Shell Acts As A Diffusional Barrier For Co2, Zhicheng Dou, Sabine Heinhorst, Eric B. Williams, C. Daniel Murin, Jessup M. Shively, Gordon C. Cannon

Faculty Publications

The widely accepted models for the role of carboxysomes in the carbon-concentrating mechanism of autotrophic bacteria predict the carboxysomal carbonic anhydrase to be a crucial component. The enzyme is thought to dehydrate abundant cytosolic bicarbonate and provide ribulose 1.5-bisphosphate carboxylase/oxygenase (RubisCO) sequestered within the carboxysome with sufficiently high concentrations of its substrate, CO₂, to permit its efficient fixation onto ribulose 1,5-bisphosphate. In this study, structure and function of carboxysomes purified from wild type Halothiobacillus neapolitanus and from a high CO₂-requiring mutant that is devoid of carboxysomal carbonic anhydrase were compared. The kinetic constants for the carbon …

Dioxidobis(2-Oxo-1,2-Dihydropyridin-3-Olato)­Molybdenum(Vi), Manoj Trivedi, Daya Pandey, Nigam Rath

Chemistry & Biochemistry Faculty Works

In the title compound, [Mo(C5H4NO2)2O2], the MoVI atom exhibits a distorted octa­hedral coordination geometry formed by two terminal oxo ligands and two monoanionic O,O-bidentate pyridinone ligands. The two terminal oxo ligands lie in a cis arrangement, the ketonic O atoms of the pyridinone ligands are coordinated trans to the oxo ligands and the deprotonated hydroxyl O atoms are located trans to each other. The crystal structure contains inter­molecular N-H...O hydrogen bonds, C-H...O contacts and face-to-face [pi]-[pi] stacking inter­actions with an inter­planar separation of 3.25 (1) Å.

Diethyl 2-[(4-Nitro­Phen­Yl)(4-Phenyl-1,2,3-Selenadiazol-5-Yl)Meth­Yl]Malonate, A. Marx, S. Saravanan, S. Muthusubramanian, V. Manivannan, Nigam Rath

Chemistry & Biochemistry Faculty Works

In the title compound, C22H21N3O6Se, the heterocyclic ring makes dihedral angles of 50.03 (11) and 67.75 (11)°, respectively, with the benzene and phenyl rings. The terminal C atoms of the ester groups are disordered over two positions: the site occupancies for the C atoms are 0.62 (3)/0.38 (3) and 0.48 (3)/0.52 (3). In the crystal structure, weak intra- and inter­molecular C-H...O inter­actions are observed.