Digital Commons Network^™

Homology Modeling And Molecular Docking For The Science Curriculum, Owen M. Mcdougal, Nic Cornia, Chris Mallory, Julia Thom Oxford, Tim Andersen

Chemistry and Biochemistry Faculty Publications and Presentations

DockoMatic 2.0 is a powerful open source software program (downloadable from sourceforge.net) that allows users to utilize a readily accessible computational tool to explore biomolecules and their interactions. This manuscript describes a practical tutorial for use in the undergraduate curriculum that introduces students to macromolecular structure creation, ligand binding calculations, and visualization of docking results. A student procedure is provided that illustrates the use of DockoMatic to create a homology model for the amino propeptide region (223 amino acids with two disulfide bonds) of collagen α1 (XI), followed by molecular docking of the commercial drug Arixtra^® to the …

Selective Anion Sensing By Chiral Macrocyclic Receptors With Multiple Hydrogen-Bonding Sites, Tadashi Ema, Keiichi Okuda, Sagiri Watanabe, Takayuki Yamasaki, Tsuyoshi Minami, Nina A. Esipenko, Pavel Anzenbacher Jr.

Chemistry Faculty Publications

Chiral macrocycles featuring sulfonamide and/or amide groups as anion-binding sites were synthesized. X-ray crystal structures and DFT calculations have shown that they adopt different conformations that may lead to unique binding behavior. Indeed, various anions could be sensed by their colorimetric and/or fluorescence signal output. The chiral macrocycles showed chiral recognition for chiral anions. Furthermore, a multisensor array with two or four chiral receptors discriminated seven phosphate anions (AMP, ADP, ATP, CMP, GMP, Pi, and PPi) with 100% classification accuracy.

Advancement Of Petroleum Diesel Alternatives Utilizing A Multifaceted And Interdepartmental Approach, Michael Morgan

UCUR

The advancement of biologically derived alternatives to petroleum diesel fuel requires a multifaceted approach. At Utah State University we use an interdisciplinary team including the Colleges of Engineering, Agriculture & Applied Sciences, and Science in conjunction with industry partners to drive innovation in improving the science behind petroleum diesel alternatives. With increasing petroleum use, depleting reserves, increasing emissions standards, and other factors, there is need for petroleum diesel alternatives that are cost effective, offer improvement, and perform similarly to petroleum diesel. Our team has focused on the use of oleaginous microbes utilizing low value effluent and waste sources including sugars …

Design And Development Of A Novel Glucose Biosensor Based On The Ferrocene-Functionalized Fe3O4 Nanoparticles/Carbon Nanotubes/Chitosan Nanocomposite Film Modified Electrode, Hua-Ping Peng, Dai-Jun Zha, Wei Chen, Ai-Lin Liu, Xin-Hua Lin

Journal of Electrochemistry

A novel platform for the fabrication of glucose biosensor was successfully constructed by entrapping glucose oxidase (GOD) in a ferrocene monocarboxylic acid-aminated Fe₃O₄ magnetic nanoparticles conjugate (FMC-AFNPs)/chitosan (CS)/multiwall carbon nanotubes (MWNTs) nanocomposite. The formation of FMC-AFNPs could effectively prevent the leakage of ferrocene and retain its electrochemical activity. This GOD/FMC-AFNPs/CS/MWNTs matrix provided a biocompatible microenvironment for retaining the native activity of the immobilized GOD. Moreover, the presence of MWNTs enhanced the charge-transport properties of the composite and facilitated electron transfer between the GOD and the electrode for the electrocatalysis of glucose. Under the optimal conditions the designed …

Responsive Polymers For Biosensing And Protein Delivery, Molla R. Islam, Yongfeng Gao, Xue Li, Michael J. Serpe

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this feature article, we review some of the most recent advances in the field of materials chemistry for biosensing, disease diagnostics, and drug delivery. Our recent work on the development of responsive polymer-based platforms for biosensing and drug delivery will also be highlighted. This feature article is meant to outline the breadth of the utility of polymer-based materials for select applications, as well as their enormous potential impact on future technologies.

Intramolecular Nitrogen Delivery For The Synthesis Of C-Glycosphingolipids. Application To The C-Glycoside Of The Immunostimulant Krn7000, Ahmad Sabri Altiti, David R. Mootoo

Publications and Research

The key reaction in this approach to C-glycosphingolipids is the stereoselective iodocyclization of a sugar-linked homoallylic carbonimidothioate. E and Z reaction substrates were assembled in a convergent fashion via an alkene metathesis strategy and exhibited the same alkene facial selectivity in the iodocyclization irrespective of alkene geometry, although the E alkene was found to be less reactive.

Mentoring Undergraduates Via Organic Synthesis, Steven L. Castle

Journal of Undergraduate Research

This report summarizes the results of the mentoring environment in my laboratory that were generated from January 2012 to present. During this period, a total of seven undergraduates performed research in my laboratory. Their names and accomplishments are listed below.

Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold

Dartmouth Scholarship

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …

Isolation And Structural Elucidation Of Cancer Therapeutic Agents In Rhamnaecae Ziziphus Obtusifolia, Matthew Woll, Dr. Noel Owen

Journal of Undergraduate Research

Many important and useful biological compounds are found in plants. Extensive work has been done on evaluating anti-cancer 1, 2, anti-malarial 3, and anti-viral 4 properties of plants. The Yaqui Indians of northern Mexico have traditionally used many natural products to cure various diseases. Gloria Moroyoqui, the daughter of a Yaqui Indian shaman (medicine man) explained to us some of the plants and their uses as medicine. The Yaqui Indians have used Rhamnacae ziziphus obtusifolia, commonly known as graythorn, as a cancer chemotherapeutic agent.

Synthesis Of Bioconjugate Dimers Used To Probe The Structure Of Pglycoprotein, Emily Parker, Dr. Merritt B. Andrus

Journal of Undergraduate Research

Chemotherapy is one of the primary treatments for cancer today. A patient’s life may depend on its efficacy, so when he or she develops multi-drug resistance (MDR) the results can be devastating. MDR, a clinical condition manifested by the failure of chemotherapy, is primarily due to the expression of P-glycoprotein (Pgp), a membrane-bound small molecule transport protein which is found normally in some cells but is greatly over expressed in drug resistant cancer cells1. It is believed that after chemotherapy drugs diffuse into the cell, Pgp effluxes them out using energy from ATP hydrolysis, thus imparting drug resistance.

Less Cookbook And More Research! Synthetic Efforts Toward Jbir-94 And Jbir-125: A Student-Designed Research Project In A Sophomore Organic Chemistry Lab, Mike A. Christiansen, C. L. Crawford, C. D. Mangum

Chemistry and Biochemistry Faculty Publications

In light of the meaningful learning gains that can be obtained through a genuine research experience, chemistry educators have had a longstanding interest in making teaching labs less “cookbook-like” and more research-driven [1]. With this mindset, we recently restructured our two-semester sophomore organic chemistry lab course to include a synthesis project that was chosen, designed, and carried out by students. This led to progress toward the syntheses of JBIR-94 and JBIR-125, two antioxidative/anticancer natural products that have yet to be assembled through organic chemistry. The major drawback of our course redesign is that it requires close supervision by an instructor …

Functional Relevance Of Acrb Trimerization In Pump Assembly And Substrate Binding, Wei Lu, Meng Zhong, Qian Chai, Zhaoshuai Wang, Linliang Yu, Yinan Wei

Chemistry Faculty Publications

AcrB is a multidrug transporter in the inner membrane of Escherichia coli. It is an obligate homotrimer and forms a tripartite efflux complex with AcrA and TolC. AcrB is the engine of the efflux machinery and determines substrate specificity. Active efflux depends on several functional features including proton translocation across the inner membrane through a proton relay pathway in the transmembrane domain of AcrB; substrate binding and migration through the substrate translocation pathway; the interaction of AcrB with AcrA and TolC; and the formation of AcrB homotrimer. Here we investigated two aspects of the inter-correlation between these functional features, …

Spectroscopic Studies Of Conformation And Packing In Polythiophenes, Edwards T. Niles

Chemistry and Chemical Biology ETDs

This thesis employs variants of spectroscopic techniques to evaluate intermolecular interactions between P3HT chains in solution and in the solid state. Emphasis was put on understanding not only how intermolecular interactions within P3HT chains affect electronic properties, but also to assess changes due to the addition of weak and strong electron acceptors. To this end, optical and magnetic spectroscopies were focused on to correlate observed changes in electronic properties to physical changes in the polymer structure. To assess changes in intermolecular interactions, self-assembly was used to form P3HT nanofibers and were studied using resonance Raman, and transient absorption, and temperature- …

Simulations Of Chemical Catalysis, Gregory K. Smith

Chemistry and Chemical Biology ETDs

This dissertation contains simulations of chemical catalysis in both biological and heterogeneous contexts. A mixture of classical, quantum, and hybrid techniques are applied to explore the energy profiles and compare possible chemical mechanisms both within the context of human and bacterial enzymes, as well as exploring surface reactions on a metal catalyst. A brief summary of each project follows.

Project 1 — Bacterial Enzyme SpvC

The newly discovered SpvC effector protein from Salmonella typhimurium interferes with the host immune response by dephosphorylating mitogen-activated protein kinases (MAPKs) with a β-elimination mechanism. The dynamics of the enzyme substrate complex of the SpvC …

Determining The Function Of Hotdog-Fold Thioesterases, Yajun Wu

Chemistry and Chemical Biology ETDs

The enzymes that hydrolyze thioesters to the free acids and free thiols are called thioesterases. Based on the different folding strategy, most thioesterases are classified into two superfamiles: the hotdog-fold enzyme superfamily or alpha/beta-fold hydrolase enzyme superfamily. Hotdog-fold thioesterases share high degree similarity in structure which resembles a hotdog'. YigI is one of the last two uncharacterized hotdog-fold thioesterases from E.coli. To study the function of YigI, substrate specificity profile was determined by thioesterase activity assay. YigI possesses a preference for long chain acyl-CoA over shorter chain acyl-CoA. The highest activity was found in catalysis of myristoyl-CoA. By alignment with …

Synthesis, Characterization, And Electrochemical Evaluation Of Novel, Highly Active Catalysts For The Oxygen Reduction Reaction In Alkaline Media, Danae Jacquelyne Davis

Chemistry and Chemical Biology ETDs

Efficient electrocatalysts for the oxygen reduction reaction (ORR) are needed for fuel cells and next generation metal-air batteries, as the overall efficiency of these systems is currently limited by cathode kinetics. While Pt and Pt-based alloys demonstrate excellent electrocatalytic activities, their prohibitive cost and rarity ultimately prevents their widespread utilization. Catalyst materials that are highly active, stable, and cost effective are needed. Manganese oxide (α-MnO₂) catalysts doped with varying amounts of Cu or Ni were synthesized, characterized, and evaluated for their performance as catalysts for the oxygen reduction reaction in alkaline electrolyte. Cu-α-MnO₂ nanowire catalysts consistently attained …

A Review Of Air–Ice Chemical And Physical Interactions (Aici): Liquids, Quasi-Liquids, And Solids In Snow, T. Bartels-Rausch, H-W Jacobi, T. F. Kahan, J. L. Thomas, E. S. Thomson, J. P. D. Abbatt, M. Ammann, J. R. Blackford, H. Bluhm, Chris Boxe, F. Domine, M. M. Frey, I. Gladich, M. I. Guzmán, D. Heger, Th. Huthwelker, P. Klán, W. F. Kuhs, M. H. Kuo, S. Maus, S. G. Moussa, V. F. Mcneill, J. T. Newberg, J. B. C. Pettersson, M. Roeselová, J. R. Sodeau

Publications and Research

Snow in the environment acts as a host to rich chemistry and provides a matrix for physical exchange of contaminants within the ecosystem. The goal of this review is to summarise the current state of knowledge of physical processes and chemical reactivity in surface snow with relevance to polar regions. It focuses on a description of impurities in distinct compartments present in surface snow, such as snow crystals, grain boundaries, crystal surfaces, and liquid parts. It emphasises the microscopic description of the ice surface and its link with the environment. Distinct differences between the disordered air–ice interface, often termed quasi-liquid …

A Review Of Air–Ice Chemical And Physical Interactions (Aici): Liquids, Quasi-Liquids, And Solids In Snow, T. Bartels-Rausch, H. -W. Jacobi, T. F. Kahan, J. L. Thomas, E. S. Thomson, J. P. D. Abbatt, M. Ammann, J. R. Blackford, H. Bluhm, C. Boxe, F. Domine, M. M. Frey, I. Gladich, M. I. Guzmán, D. Heger, Th. Huthwelker, P. Klán, W. F. Kuhs, M. H. Kuo, S. Maus, S. G. Moussa, V. F. Mcneill, J. T. Newberg, J. B. C. Pettersson, M. Roeselová, J. R. Sodeau

Chemistry Faculty Publications

Snow in the environment acts as a host to rich chemistry and provides a matrix for physical exchange of contaminants within the ecosystem. The goal of this review is to summarise the current state of knowledge of physical processes and chemical reactivity in surface snow with relevance to polar regions. It focuses on a description of impurities in distinct compartments present in surface snow, such as snow crystals, grain boundaries, crystal surfaces, and liquid parts. It emphasises the microscopic description of the ice surface and its link with the environment. Distinct differences between the disordered air–ice interface, often termed quasi-liquid …

The Location And Role Of Phosphate In Horse Spleen Ferritin (Hosf), Joseph Johnson

Journal of Undergraduate Research

Although iron Is necessary for life, It Is toxic If left free In most organIsms. To control Its toxic effects and still have iron available for biological use, organisms use ferrltins. Ferritins are similar throughout the biological world. Each ferritin is a roughly spherical, hollow protein with a thin, negatively charged shell that can hold up to 4500 Iron atoms. This shell is composed of 24 nearly Identical subunits. Junctions between three or four subunits form channels, 3-fold or 4-fold respectively, that traverse the protein shell. The hydrophilic 3-fold channels are believed to be the key pathway for the uptake …

Phosducins: Evidence For The Evolution Of New Proteins Through Gene Duplication, Tim Rand, Dr. Barry Willardson

Journal of Undergraduate Research

The theory of evolution by natural selection is arguably the most important scientific theory ever formulated. Its importance has not been manifest in an “ooh, ah” technological way—it doesn’t empower us to fly airplanes or to illuminate streets at night—but no scientist really thinks technology is the sine qua non of science anyway. The really big theories are the ones that change our thinking, rather than the way we get around or see at night. The theory of evolution changed the way we think about life itself. Interestingly, our acceptance of evolution is based mainly on its elegance. As far …

Synthesis Of Systematically Varied Nucleosides As A Logical Approach Toward Inhibitor Design For Nucleoside Transport Proteins, Lars P. C. Nielsen, Dr. Morris J. Robins

Journal of Undergraduate Research

Glucose transporter proteins constitute one class of transmembrane integral proteins that have received much attention in the current chemical literature. Many prominent groups have set out to explore their mechanisms, kinetics, and active sites. Studies have focussed on one of these in particular, Human Glucose Transporter I, the most common and efficient at mediating cellular glucose concentrations. Studies have also proven that certain nucleoside transporters exist, analogous to the sugar proteins, which regulate nucleoside and nucleotide concentrations in cells.

A Novel Human Angiotensin Ii Type 1 Receptor Isoform Elicits An Exaggerated Angiotensin Ii-Induced Response, Terry S. Elton, Dr. James W. Ogilvie Jr.

Journal of Undergraduate Research

Hypertension (i.e., high blood pressure) is a significant health problem affecting more than 15% of the population contributing to the increased incidence of heart failure, kidney failure and stroke. The renin-angiotensin system (RAS) plays a pivotal role in salt and water homeostasis and the maintenance of vascular tone. This balance is achieved through the actions of the hormone, angiotensin II (Ang II), the biologically active component of the RAS, with its membrane-bound receptors. These receptors, designated as type 1 and type 2 (AT1R and AT2R), bind Ang II with equal affinity. The AT1R, however, which is localized in numerous tissues …

Expression, Activity And Inhibition Of Canine Cyclooxygenase, Joel Ellis Wilson, Dr. Dan Simmons

Journal of Undergraduate Research

Nonsteroidal anti-inflammatory drugs (NSAIDs) exhibit their effect by inhibiting the cyclooxygenase (COX) enzymes. However, inhibition of both COX-1 and COX-2 by the administration of NSAIDs to both humans and animals often leads to negative side effects, most commonly gastric toxicity, including ulcers, which may progress to perforation with risk of sepsis. Functional COX-1 and COX-2 are both necessary to maintain the integrity of the gastrointestinal lining. Fueled by the discovery of COX-2 and the elucidation of its biological properties, new NSAIDs have been produced that selectively inhibit only COX-2. This new class of inhibitors effectively reduces pain and inflammation with …

A Partial Asymmetric Synthesis Of The Anti-Tumor Antibiotic Geldanamycin, Bryon Simmons, Dr. Merritt B. Andrus

Journal of Undergraduate Research

Geldanamycin, a member of the benzoquinoid ansamycin family, was discovered in 1970 by workers at UpJohn laboratories.1 Scientists were eager to characterize and assess the biological activity of this natural product, first isolated from the bacteria species Steptomyces hygroscpius.2 It was soon learned that geldanamycin functioned as an antibiotic. More importantly, this antibiotic was also shown to check the proliferation of malignant cancer cells.3 This observation has fueled significant interest in geldanamycin as a potential antitumor drug.

Crucial Positively Charged Residues For Ligand Activation Of The Gpr35 Receptor, Pingwei Zhao, Tom R. Lane, Helen G.L. Gao, Dow P. Hurst, Evangelia Kotsikorou, Long Le, Eugen Brailoiu, Patricia H. Reggio, Mary E. Abood

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

GPR35 is a G protein-coupled receptor expressed in the immune, gastrointestinal, and nervous systems in gastric carcinomas and is implicated in heart failure and pain perception. We investigated residues in GPR35 responsible for ligand activation and the receptor structure in the active state. GPR35 contains numerous positively charged amino acids that face into the binding pocket that cluster in two distinct receptor regions, TMH3-4-5-6 and TMH1-2-7. Computer modeling implicated TMH3-4-5-6 for activation by the GPR35 agonists zaprinast and pamoic acid. Mutation results for the TMH1-2-7 region of GPR35 showed no change in ligand efficacies at the K1.32A, R2.65A, R7.33A, and …

Deconstructing A Plant Macromolecular Assembly: Chemical Architecture, Molecular Flexibility, And Mechanical Performance Of Natural And Engineered Potato Suberins, Olga Serra, Subhasish Chatterjee, Merce Figueras, Marisa Molinas, Ruth E. Stark

Publications and Research

Periderms present in plant barks are essential protective barriers to water diffusion, mechanical breakdown, and pathogenic invasion. They consist of densely packed layers of dead cells with cell walls that are embedded with suberin. Understanding the interplay of molecular structure, dynamics, and biomechanics in these cell wall-associated insoluble amorphous polymeric assemblies presents substantial investigative challenges. We report solid-state NMR coordinated with FT-IR and tensile strength measurements for periderms from native and wound-healing potatoes and from potatoes with genetically modified suberins. The analyses include the intact suberin aromatic; aliphatic polymer and cell-wall polysaccharides, previously reported soluble depolymerized transmethylation products, and undegraded …

On Chip Preconcentration And Labeling Of Protein Biomarkers Using Monolithic Columns, Device Fabrication, Optimization, And Automation, Rui Yang

Theses and Dissertations

Detection of disease specific biomarkers is of great importance in diagnosis and treatment of diseases. Modern bioanalytical techniques, such as liquid chromatography with mass spectrometry (LC-MS), have the ability to identify biomarkers, but their cost and scalability are two main drawbacks. Enzyme-linked immunosorbent assay (ELISA) is another potential tool, but it works best for proteins, rather than peptide biomarkers. Recently, microfluidics has emerged as a promising technique due to its small fluid volume consumption, rapidness, low fabrication cost, portability and versatility. Therefore, it shows prominent potential in the analysis of disease specific biomarkers. In this thesis, microfluidic systems that integrate …

Nickel-Catalyzed Cross-Coupling Reactions Involving Secondary And Tertiary Alkyl Nucleophiles, Amruta Ajit Joshi

Dissertations, Theses, and Capstone Projects

In the first chapter, introduction of transition metal-catalyzed cross-coupling reactions has been given. These transition metal-catalyzed C-C bond forming reactions have been used extensively in organic synthesis. Among them, C(sp2)-C(sp2) bond forming reactions have been widely studied over decades. More recently, some reports have demonstrated the use of C(sp3) nucleophiles and electrophiles in cross-coupling reactions. However, use of secondary and tertiary alkyl nucleophiles has remained a challenge due to competitive β-hydride elimination and slow transmetallation of bulky secondary and tertiary alkyl organometallic nucleophiles.

In the second chapter, the first general nickel-catalyzed Negishi reaction for the cross-coupling of unactivated, acyclic secondary …

An Abundant Dysfunctional Apolipoprotein A1 In Human Atheroma, Ying Huang, Joseph A. Didonato, Bruce S. Levison, Dave Schmitt, Lin Li, Yuping Wu, Jennifer Buffa, Timothy Kim, Gary S. Gerstenecker, Xiaodong Gu, Chandra S. Kadiyala, Zeneng Wang, Miranda K. Culley, Jennie E. Hazen, Anthony J. Didonato, Xiaoming Fu, Stela Z. Berisha, Daoquan Peng, Truc T. Nguyen, Shaohong Liang, Chia-Chi Chuang, Leslie Cho, Edward F. Plow, Paul L. Fox, Valentin Gogonea, W.H. Wilson Tang, John S. Parks, Edward A. Fisher, Jonathan D. Smith, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl− system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding …

Conformational Features Of The Human U2-U6 Snrna Complex, Ravichandra Bachu

Dissertations, Theses, and Capstone Projects

The splicing of precursor messenger (pre-m) RNA, during which noncoding intervening sequences are excised and flanking coding regions ligated, is an integral reaction of gene expression. In eukaryotes, it is carried out by a dynamic RNA-protein complex called the spliceosome, in which five small nuclear (sn) RNA components are actively involved in recognition and chemical aspects of the process. A complex formed between U2 and U6 snRNAs is implicated in the chemistry of pre-mRNA splicing. The catalytic activity of the U2-U6 snRNA complex is dependent on the presence of Mg2+ ions, and the complex has been shown to have several …