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Optimization And Implementation Of Entrapment: A Novel Immobilization Technique For High-Performance Affinity Chromatography, Abby J. Jackson

Department of Chemistry: Dissertations, Theses, and Student Research

The proper use of high performance affinity chromatography (HPAC) in the study of biologically-related systems requires that careful attention be paid to the nature in which the affinity ligand is incorporated into the stationary phase.  Ideally, the behavior of the immobilized ligand should mimic the behavior of the ligand in its natural environment.  Retaining the soluble form of the ligand, by avoiding covalent immobilization completely, is one effective way to retain the activity of the ligand.  Previously, noncovalent immobilization techniques that do not modify the ligand of interest have included physical entrapment onto low performance supports.

This dissertation introduces an …

Drug Design, Biological Activity, And Metabolic Consequences Of Cytotoxic Platinum Compounds: Utilizing Fluorescent Tagging To Understand Drug Action And Metabolism, Brad Benedetti

Theses and Dissertations

Platinum drugs are among the most commonly used chemotherapeutics for the treatment of testicular, head and neck, ovarian, small cell lung, and colorectal carcinomas. Although the current set of platinum chemotherapeutics has proven somewhat successful, the overall success of platinum based drugs is limited due to acquired drug resistance and a limited range of tumor types that are treatable with the current regime. The development of novel cytotoxic platinum based compounds, both trans- and polynuclear, provides for the promising treatment of clinical platinum drug resistant tumors. While the cytotoxic activity of platinum drugs provides for a hopeful outlook, the ultimate …

A Global Assessment Of Gold, Titanium, Strontium And Barium Pollution Using Sperm Whales (Physeter Macrocephalus) As An Indicator Species, John Pierce Wise Sr., W. Douglas Thompson, Sandra S. Wise, Carolyne Lacerte, James Wise, Christy Gianios Jr., Christopher Perkins, Tongzhang Zheng, Lucille Benedict Phd, Michael D. Mason, Roger Payne, Iain Kerr

Department of Chemistry

This study provides a global baseline for barium, gold, titanium and strontium as marine pollutants using the sperm whale (Physeter macrocephalus) as an indicator species. Barium, gold, titanium and strontium are metals that are little studied in marine environments. However, their recent emergence as nanomaterials will likely increase their presence in the marine environment. Moreover, nanosized particles are likely to exhibit toxic outcomes not seen in macrosized particles. Biopsies from free ranging sperm whales were collected from around the globe. Total barium levels were measured in 275 of 298 sperm whales tested for barium and collected from 16 regions around …

Optimization Of Multiplex Pcr For Multiple Locus Variable Number Tandem Repeat Analysis For Salmonella Typhimurium, George Hafez, Remington Turner, Andrea Haskett, Rajesh Nagarajan

College of Arts and Sciences Poster Presentations

Salmonella typhimurium infects an estimated 1.4 million in the United States and kills over five hundred annually.  The current way of categorization, Pulse Field Gel Electrophoresis (PFGE) and antibiotic sensitivity testing, lack the ability to distinguish between some closely related strains.  We are attempting to optimize a new technique of categorization, Multiple Locus Variable number tandem repeat Analysis (MLVA).  We made changes to temperature and concentration variables within the multiplex PCR procedure to streamline the identification process.  By optimizing the multiplex PCR procedure we intend to create more consistent amplification of the loci used in MLVA analysis, which will improve …

Monitoring The Electrochemical Activity Of Biological Samples Using Scanning Electrochemical Microscopy, Erica Woodall, Melinda Baur, Faculty Advisor

John Wesley Powell Student Research Conference

The goal of the project is to develop the Scanning Electrochemical Microscopy (SECM) as a tool to study the biological effects of oxidative damage on rat pheochromocytoma cells (PCI2 cells). SECM is a useful tool for the analysis of biological samples because the ultramicroelectrode tip of the probe can detect the presence of electrochemically active compounds such as neurotransmitters, particularly dopamine and norepinephrine, while simultaneously characterizing the topography of the cell. The topography of the cell was determined by maintaining a constant distance between the tip of the electrode and the surface of the cell. In the collector mode, the …

The Low Resolution Structure Of Apoa1 In Spherical High Density Lipoprotein Revealed By Small Angle Neutron Scattering, Zhiping Wu, Valentin Gogonea, Xavier Lee, Roland P. May, Vitaliy Pipich, Matthew A. Wagner, Arundhati Undurti, Thomas C. Tallant, Camelia Baleanu Gogonea, Francesca Charlton, Alexander I. Ioffe, Joseph A. Didonato, Kerry Anne Rye, Stanley L. Hazen

Chemistry Faculty Publications

Spherical high density lipoprotein (sHDL), a key player in reverse cholesterol transport and the most abundant form of HDL, is associated with cardiovascular diseases. Small angle neutron scattering with contrast variation was used to determine the solution structure of protein and lipid components of reconstituted sHDL. Apolipoprotein A1, the major protein of sHDL, forms a hollow structure that cradles a central compact lipid core. Three apoA1 chains are arranged within the low resolution structure of the protein component as one of three possible global architectures: (i) a helical dimer with a hairpin (HdHp), (ii) three hairpins (3Hp), or (iii) an …

Chemistry & Biochemistry Newsletter, Department Of Chemistry & Biochemistry, South Dakota State University

Chemistry & Biochemistry Newsletter: 2002-2015

Inside:

Page 2 Chemistry Professor Recognized for Instructional Excellence: Studies How Students Learn

Page 3 CBC Scientist Decorated for Service in Antarctica

Page 4 Department of Defense Graduate Fellowship Awards Will Help Fund Cyanide Research

Page 5 3M Foundation invests $250,000 in Freshman Chemistry; Recent Publications and Grants

Page 6 NIH RO1 Grant Will Address Congestive Heart Failure

Page 7 Scholarship Award Winners; 2010-2011 Chemistry Graduates

Page 8 Student Research Focuses on Soil Health

Sequencing Of Amine Nucleoside Polymers: Understanding The Fidelity Of Dna-Directed Reductive Amination, Sarah M. Anderson

Honors Student Works

DNA replication is a form of template-directed polymerization that occurs with the aid of numerous enzymes. By developing a DNA replication mimic that can undergo template-directed polymerization without enzymes, the scope of template-directed polymerization will be broadened beyond biological systems. One template-directed polymerization method that has proven successful is reductive amination on a DNA template, a two-step polymerization reaction involving equilibrium imine formation followed by reduction of the imine to the amine. Because DNA-directed reductive amination is an information transfer system, it should proceed with fidelity; however, the extent of fidelity must be explored. These studies will require the ability …

Increasing Binding Strength For Capsaicin Analogs Through Alteration Of Lanthanide Chelates, R. Kruger Bressin, Christopher G. Gulgas

Theses & Honors Papers

Capsaicin is the molecule in peppers that produces a sensation of heat and pain when exposed to sensory nerve cells in the body. A series of ethylenediaminetetracetate bis­amide chelates have been synthesized with regions selective for capsaicinoid binding to determine which functional groups increase overall binding strength. The initial lanthanide complexes bound capsaicinoids with moderate strength (approximately 105 M" 1). Additions to the bis-amide region of the chelating ligand aim to increase the selectivity of the lanthanide complex for capsaicinoids. Derivatives have been synthesized that contain aromatic rings and carbon chains to augment binding strength via the hydrophobic effect. Upon …

Dna Barcoding Of Sea Turtle Leeches (Ozobranchus Spp.) In Florida Coastal Waters, Triet Minh Truong, Audrey E. Mcgowin Ph.D.

Chemistry Student Publications

Fibropapillomatosis (FP) is a neoplastic disease originally identified only on green sea turtles (Chelonia mydas). The disease is likely to be terminal if tumors are developed internally, but external tumors on the eyes, mouth, and flippers can also lead to fatal impairment of vision and difficulty feeding and swimming. The involvement of an environmental cofactor appears possible since many FP outbreaks occur at sites of poor water quality in Florida, Hawaii, Brazil, and other similar places around the world, but outbreaks have also been recorded at less contaminated sites. Studies have shown an association between FP and the fibropapilloma-associated turtle …

Engineering Cooperative Tecto-Rna Complexes Having Programmable Stoichiometries, Neocles B. Leontis, Irina V. Novikova, Bachar H. Hassan, Marina G. Mirzoyan

Chemistry Faculty Publications

High affinity and specificity RNA-RNA binding interfaces can be constructed by combining pairs of GNRA loop/loop-receptor interaction motifs. These interactions can be fused using flexible four-way junction motifs to create divalent, self-assembling scaffolding units ('tecto-RNA') that have favorable properties for nanomedicine and other applications. We describe the design and directed assembly of tecto-RNA units ranging from closed, cooperatively assembling ring-shaped complexes of programmable stoichiometries (dimers, trimers and tetramers) to open multimeric structures. The novelty of this work is that tuning of the stoichiometries of self-assembled complexes is achieved by precise positioning of the interaction motifs in the monomer units rather …

Synthesis And Analytical Evaluation Of Folate Conjugates For Use In Cancer Cell Detection, Rakeshkumar V. Desai

All Capstone Projects

Folate receptors have two glycosyl phosphatidylinositol anchored isomers, alpha and beta. Folate receptor alpha binds with high affinity for folic acid and act as a receptor for mediated transport of folate into the cells. Folate is necessary for DNA metabolism and thus it is speculated that rapidly dividing cancer cells have an increased necessity for folic acid. Folate receptor alpha levels eminent in specific malignant diseases (like solid tumors and leukemia) and thus folate receptors serve in the detection of FR+ (Folate receptor positive) and diagnosis of cancers.

In general, liposomes have the capacity intake the most imaging and toxic …

Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae, J. S. Smith, Q. Chen, Liliya A. Yatsunyk, John Michael Nicoludis , '12, M. S. Garcia, R. Kranaster, S. Balasubramanian, D. Monchaud, M.-P. Teulade-Fichou, L. Abramowitz, D. C. Schultz, F. B. Johnson

Chemistry & Biochemistry Faculty Works

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show …

Section Abstracts: Chemistry

Virginia Journal of Science

Abstracts of the Chemistry Section for the 89th Annual Meeting of the Virginia Academy of Science, May 25-27, 2011, University of Richmond, Richmond VA.

Detection Of Folate Binding Protein, Anwer Unnisa

All Capstone Projects

Cancer is the second leading cause of death despite the anti cancer developments including hormone therapy, radiotherapy, chemotherapy. Chemotherapy includes use of potent drugs such as camptothecin, paclitaxel and mitomycin. These drugs have an effect which is dose responsive, where the drug exposure and cell kill are proportional. This chemotherapy is high dose and has less selectivity for cancer cells and has more toxic effect to normal cells. Such kind of non specific treatment to tumor is causing hurdles in the treatment of cancer by chemotherapy. To overcome this current limitation to chemotherapy, the anti cancer drug with high specificity …

Synthesis And Characterization Of Nanoparticulated Rifampicin, Lakshmi Sai Priyanka Guttikonda

All Capstone Projects

Rifampicin is a naturally made, non-peptide antibiotic. It is bactericidal, killing by disabling the protein expression system universally conserved by all bacteria. Specifically, it inhibits the RNA polymerase protein, which is responsible for binding to a strand of DNA as a template and using it to construct a strand of mRNA. The reason rifampicin works so well is that it is a rigid molecule, and sits tightly in the pocket where it binds, allowing the bonds to be very strong. However, this also means if an amino acid with the edge of the channel with a small side chain is …

Purification And Analysis Of Folate Dye Conjugates, Anisha Hari Ganji

All Capstone Projects

Folate receptors play an important role in drug delivery systems as they are known to increase the potency and reduce toxicity of many cancer therapies. Folate receptors are present in abundance on cancerous tissues more so than on non-cancerous tissues. Folate binds to a variety of drugs that include chemotherapeutic agents, liposomes, radio-imaging agents, immunotherapeutic drugs and the like. Folate has been researched and used over the past decade as it is inexpensive and binds to the folate receptors with high affinity when compared to monoclonal antibodies. Nuclear imaging by SPECT and PET has interested many researchers. Other processes include …

Evaluation And In Vitro Studies Of Folate-Peg-Biotin, Kuldeep Reddy Vanga

All Capstone Projects

Folate receptor is a membrane bound protein which is highly expressed by cancer cells and macrophages. Folic acid is required for the normal growth of cells and it has been found that rapidly growing cancer cells require high levels of folic acid. Folic acid binds to folate receptors and through receptor mediated transport folate enters cells. This property has been used to synthesize a probe using folate as ligand through polyethylene glycol-Biotin linker. This can be used to attach a drug which is ultimately delivered at the site of infectious cells. The study involved here was to determine how folate …

Benchmarking The Pharmaceutical Industry: A Briefing On An Irish Research Study, Nuala Calnan (Editor)

Conference Papers

This paper presents an Irish research study currently being undertaken by the Pharmaceutical Regulatory Science Team at the Dublin Institute of Technology (DIT) into the impact of new pharmaceutical regulatory guidance on the development and manufacture of medicinal drug products.

It launches a Pharmaceutical Industry Benchmarking Questionnaire designed to assess the impact and level of implementation of the ICH Tripartite Quality Guidance Q8, Q9 and Q10.

Non-Esterified Fatty Acids Generate Distinct Low-Molecular Weight Amyloid-Β (Aβ42) Oligomers Along Pathway Different From Fibril Formation, Amit Kumar, Rebekah L. Bullard, Pritesh Patel, Lea C. Paslay, Dipti Singh, Ewa A. Bienkiewicz, Sarah E. Morgan, Vijayaraghavan Rangachari

Faculty Publications

Amyloid-beta (A beta) peptide aggregation is known to play a central role in the etiology of Alzheimer's disease (AD). Among various aggregates, low-molecular weight soluble oligomers of A beta are increasingly believed to be the primary neurotoxic agents responsible for memory impairment. Anionic interfaces are known to influence the A beta aggregation process significantly. Here, we report the effects of interfaces formed by medium-chain (C9-C12), saturated non-esterified fatty acids (NEFAs) on A beta 42 aggregation. NEFAs uniquely affected A beta 42 aggregation rates that depended on both the ratio of A beta:NEFA as well the critical micelle concentration (CMC) of …

A Three Dimensional Green's Function Solution Technique For The Transport Of Heavy Ions In Laboratory And Space, Candice Rockell Gerstner

Mathematics & Statistics Theses & Dissertations

In the future, astronauts will be sent into space for longer durations of time compared to previous missions. The increased risk of exposure to ionizing radiation, such as Galactic Cosmic Rays and Solar Particle Events, is of great concern. Consequently, steps must be taken to ensure astronaut safety by providing adequate shielding. The shielding and exposure of space travelers is controlled by the transport properties of the radiation through the spacecraft, its onboard systems and the bodies of the individuals themselves. Meeting the challenge of future space programs will therefore require accurate and efficient methods for performing radiation transport calculations …

Bioinformatics, Thermodynamics And Kinetics Analysis Of An All Alpha Helical Protein With A Gree-Key Topology, Hai Li

Chemistry & Biochemistry Theses & Dissertations

Computational and experimental studies focusing on the role of conserved residues for folding and stability is an active and promising area of research. To further expand our understanding we present the results of a bioinformatics analysis of the death domain superfamily. The death domain superfamily fold consists of six α-helices arranged in a Greek-key topology, which is shared by the all β-sheet immunoglobulin and mixed α/β-plait superfamilies. Our sequence and structural studies have identified a group of conserved hydrophobic residues and corresponding long-range interactions, which we propose are important in the formation and stabilization of the hydrophobic core and native …

Synthetic And Mechanistic Studies On The Cross-Coupling Reactions Catalyzed By Ruthenium Complexes, Ruili Gao

Dissertations (1934 -)

Transition metal catalyzed C-H bond activation reaction is a powerful synthetic method for forming functionalized products directly from unreactive hydrocarbons, and has enormous synthetic potentials for developing chemical processes ranging from petroleum products to pharmaceutical agents. In an attempt to mimic the high stereo selectivity and region selectivity of catalytic reactions by transition metal catalysts, recent research has focused on design and synthesis of transition metal complex and the application on the coupling reactions involving C-H bond activation.

Herein, we wish to report the highly effective coupling reactions involving C-H bond activation by using well-defined ruthenium catalysts. Ruthenium hydride complex …

N5-Phosphonoacetyl-L-Ornithine (Palo): A Convenient Synthesis And Investigation Of Influence On Regulation Of Amino Acid Biosynthetic Genes In Saccharomyces Cerevisiae, Brad Johnson, Rachel Steadman, Krista D. Patefield, Jeffrey J. Bunker, Audrey L. Atkin, Patrick Dussault

Patrick Dussault Publications

A scalable four-step synthesis of the ornithine transcarbamylase inhibitor N⁵-phosphonoacetyl-L-ornithine (PALO) is achieved through boroxazolidinone protection of ornithine. Investigations in the model organism Saccharomyces cerevisiae found that, in contrast to a previous report, PALO did not influence growth rate or expression of genes involved in arginine metabolism.

Organometallic Iron(Iii)-Salophene Exerts Cytotoxic Properties In Neuroblastoma Cells Via Mapk Activation And Ros Generation, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Richard G. Moore, Laurent Brard, Thilo S. Lange

Chemistry Faculty Publications and Presentations

The objective of the present study was to investigate the specific effects of Iron(III)-salophene (Fe-SP) on viability, morphology, proliferation, cell cycle progression, ROS generation and pro-apoptotic MAPK activation in neuroblastoma (NB) cells. A NCI-DTP cancer screen revealed that Fe-SP displayed high toxicity against cell lines of different tumor origin but not tumor type-specificity. In a viability screen Fe-SP exhibited high cytotoxicity against all three NB cell lines tested. The compound caused cell cycle arrest in G1 phase, suppression of cells progressing through S phase, morphological changes, disruption of the mitochondrial membrane depolarization potential, induction of apoptotic markers as well as …

Developing Novel Nanoparticulated Imaging System Using Luminescence Enhancement Of Eu(Iii) And Tb(Iii) By Single-Strand Dna Encapsulation, David A. Corcoran, Diana L. Harms (Galindo)

All Student Theses and Dissertations

Non-toxic biosensors are encountering an increase in attention for use in understanding the fate of cells and as a diagnostic tool. Development and incorporation of suitable fluorophores into biological molecules is the key for monitoring proteins in vivo research. This study investigated the enhanced emission of Eu (III) and Tb (III) upon binding to the four DNA bases and their respective nucleotides, found the best ratio for effective energy transfer, and developing nanoparticles to deliver the biosensor into the cells.

It is well known that Eu (III) and Tb (III) exhibit very distinctive photo-characteristics. The luminescence of these two lanthanides …

Computational Investigation Of The Bioactive Selenium Compounds Ebselen And Selenious Acid, Sonia Antony

Chemistry & Biochemistry Theses & Dissertations

Selenium, a toxic element, is required in trace quantities for the proper functioning of biological systems. The experimental mechanistic study of the reactions of ebselen and selenious acid is difficult due to complexity of the reaction mixtures and the presence of short-lived intermediates. Computational modeling of the reactivity of these species can give us an insight into their mechanisms, but the process is complicated by proton exchanges associated with the mechanistic steps. In gas phase modeling, this may be corrected to a certain level using the solvent assisted proton exchange (SAPE) method. SAPE is a modeling technique that mimics solvent …

Electrospinning Fabrication, Structural And Mechanical Characterization Of Rod-Like Virus-Based Composite Nanofibers, Laying Wu, Jianfeng Zang, L. Andrew Lee, Zhongwei Niu, Gary C. Horvatha, Vaughn Braxtona, Arief C. Wibowo, Michael A. Bruckman, Soumitra Ghoshroy, Hans-Conrad Zur Loye, Xiaodong Li, Qian Wang

Faculty Publications

Tobacco mosaic virus (TMV) was electrospun with polyvinyl alcohol (PVA) into continuous TMV–PVA composite nanofibers to form a biodegradable nonwoven fibrous mat as an extracellular matrix (ECM) mimetic. Morphological characterizations by electron microscopyshowed that the addition of varying amounts of TMV resulted in homogeneous nanofibers without phase separation and did not change the diameter of the composite nanofibers. The orientation of TMV in as-spun fibers could be readily controlled and post-processing of the nonwoven TMV–PVA mat significantly improved its water resistance. In addition, tensile tests were performed on individual nanofibers, which revealed that the TMV–PVA composite nanofibers achieved a comparable …

Human Endogenous Sodium Pump Inhibitors Measurement, Source, Synthesis And Regulation, Jie Ma

Theses and Dissertations

The sodium pump (SP or Na+,K+-ATPase) is a membrane embedded protein complex that pumps 3 sodium ions out and 2 potassium ions into the cell per cycle and in so doing creates a cell membrane electrochemical potential. The membrane potential is critical for any functional cell. In the vasculature, reduction in the voltage potential causes vascular smooth muscle contraction and a narrowing of blood vessels (vasoconstriction) which can lead to increased blood pressure (hypertension). Substantial research over the past several decades has provided a vast amount of research on SP inhibitors, sometimes called endogenous digitalis-like factors (EDLF). Increased levels of …

Super Collision Energy Transfer Studies In Single Collisions Between Vibrationally Hot Benzene Like Molecules And Ground State Bath Molecules: The Effect Of Physical Properties Of Donor And Bath Molecules On Super Collision Energy Transfer, Kilyoung Kim

Theses and Dissertations

This research is focused on single-collision energy transfer events between highly vibrationally excited benzene-like donor molecules and small bath molecules, CO2 and N2O in the vibrational ground level. Measuring how much energy is transferred from donors to bath molecules was accomplished by probing bath molecules scattered into specific-rotational states using a tunable Δv=0.0003 cm-1 solid state diode laser. The normalized energy transfer probability distribution function, P(E,E'), determined from energy gain information, is very useful in comparing collisional energy transfer efficiency between various collision systems. P(E,E') is also used to investigate the effects of donor and bath physical properties on collisional …