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Articles 1 - 19 of 19

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Computational Studies Of Paradifluorobenzene Cations And Hydrogen Cyanide Molecule, John C. Rowe Iv Jan 2016

Computational Studies Of Paradifluorobenzene Cations And Hydrogen Cyanide Molecule, John C. Rowe Iv

Honors Theses

Polycyclic aromatic hydrocarbons (PAHs) are hypothesized to comprise a significant portion of interstellar carbon identified from the Diffuse Interstellar Bands (DIBs). Gas phase cation-molecule reactions between compounds that previously existed as weakly bound species provides the best explanation for the emergence of PAHs in the interstellar medium (ISM). In this work, we use computational methods to characterize one of these weakly-bound systems. We discovered that intramolecular charge distribution (calculated using the Natural Population Analysis) dictate the complexes formed between a paradifluorobenzene cation and either one or two HCN molecules. Additionally, the relative stabilities of the complexes and the binding energies ...


Characterization Of Catecholamine Receptors And Transporters In Murine Macrophages, Elizabeth Gonye Jan 2016

Characterization Of Catecholamine Receptors And Transporters In Murine Macrophages, Elizabeth Gonye

Honors Theses

Macrophages are a critical part of the immune response. When circulating monocytes move into tissues they differentiate int macrophages to mount the first line of defense against pathogens.


Calcium (Ii) Catalyzed Nitrone Additions, Elizabeth A. Congdon Jan 2016

Calcium (Ii) Catalyzed Nitrone Additions, Elizabeth A. Congdon

Honors Theses

Calcium(II) complexes have be shown to be successful catalysts for nitrone reactions. The addition of n-­‐methyl and n-­‐phenyl nitrones to donor-­‐acceptor cyclopropanes was achieved with calcium triflate (Ca(OTf). Differentially substituted tetrahydro-­‐1,2-­‐oxazines were synthesized in good to excellent yields. Calcium triflate was also found to catalyze the addition of silyl enol ethers to n-­‐phenyl nitrones along the Mukaiyama-­‐Mannich addition pathway. B-­‐amino carbonyls were synthesized from a variety of substituted nitrones. Bulky and cyclic silyl enol ethers were also found to be reactive, the products of which were isolated in good ...


Impact Of Vector Range Expansion On Pathogen Transmission Dynamics Of Lyme Disease In Southwestern Virginia, Bishan Bhattarai Jan 2016

Impact Of Vector Range Expansion On Pathogen Transmission Dynamics Of Lyme Disease In Southwestern Virginia, Bishan Bhattarai

Honors Theses

Blacklegged ticks, Ixodes scapularis is the primary vector of Lyme disease in eastern United States. Borrelia Burgdorfei, the etiological agent of Lyme disease is transferred by ticks of Ixodes species. In recent years, its congener, Ixodes affinis has been expanding its range northwards from its southern population. We were interested in studying how the introduction of this new vector affected the interaction between the pathogen genotype and the host. We hypothesized that differential host use by I. affinis and I. scapularis would partly explain observed differences in B. burgdorferi infection prevalence and genotypic structure in southeastern Virginia. The result from ...


Development Of A Genetic Over-Expression System For The Freshwater Sponge Ephydatia Muelleri, Joe Walsh Jan 2015

Development Of A Genetic Over-Expression System For The Freshwater Sponge Ephydatia Muelleri, Joe Walsh

Honors Theses

The aim of this work is to develop an over-expression system for Ephydatia muelleri. Preliminary work by Klaske Schippers (Schippers, 2013) showed sponges were induced to transcribe reporter genes driven by the widely used cytomegalovirus promoter (CMV). Building off Schippers work, newly identified native Ephydatia promoters were identified from the genome and verified to drive expression ofreporter genes. Validated over-expression vectors and transfection technology will allow researchers around the world who are working with this organism to ask questions about cell specification, gene regulation and animal development.


An Nmr-Guided Approach To The Isolation Of Secondary Metabolites From Nrps And Pks Gene Clusters, Connor Craig Jan 2015

An Nmr-Guided Approach To The Isolation Of Secondary Metabolites From Nrps And Pks Gene Clusters, Connor Craig

Honors Theses

Secondary metabolites continue to offer a promising source of novel chemical entities with therapeutic bioactivities. Our research aims to isolate secondary metabolites produced by non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) constructs. A metagenomic library was created from the marine bacterium Pseudoalteromonas sp., which was isolated from the Chesapeake Bay sponge Halichondria bowerbanki. Using a functional screen for PPTase activity we were able to identify colonies that contained NRPS and PKS gene clusters. Cultures of this microbe have been produced and analyzed using a combination of chromatography and 1H, 13C, HMBC, HSQC, COSY, AND NOESY NMR spectra. We were ...


Isolation Of Microbial Nrps And Pks Gene Clusters For Natural Product Isolation, Danielle N. O'Hara Jan 2015

Isolation Of Microbial Nrps And Pks Gene Clusters For Natural Product Isolation, Danielle N. O'Hara

Honors Theses

Greater than 99% of microbes living in the environment are uncultivable due to their complex nutrient and temperature requirements for growth. These microorganisms present a potential source of natural products that could be developed for biotechnological and pharmaceutical uses. Microorganisms with phosphopantetheinyl transferase (PPTase) activity are of high interest due to the role PPTase plays in activating non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) gene clusters. These gene clusters produce multi-enzymatic, multi-domain megasynthases that produce complex natural products utilized by the host organism for selective advantages. This study isolated genomic DNA from soil samples collected from the University of ...


One-Pot Heteroconjugate Addition-Diels-Alder Reactions And Acetate-Catalyzed Aldol Reactions Of Α-Silyl Nitriles, Carly Mueller Jan 2014

One-Pot Heteroconjugate Addition-Diels-Alder Reactions And Acetate-Catalyzed Aldol Reactions Of Α-Silyl Nitriles, Carly Mueller

Honors Theses

  1. A one-pot three-step Diels–Alder reaction sequence of ethyl propiolate and thiols can be performed to produce high yields of complex bicyclic products. A KOt-Bu-catalyzed thioconjugate addition of thiols to enoates, oxidation of the generated thioenoate by mCPBA, and Li-catalyzed Diels–Alder addition of cyclopentadiene occur in situ, without any purification of intermediates.
  2. Stereoselectivity of the Diels–Alder product was examined by utilizing a chiral sulfone substrate. It was determined that these substrates were unable to provide significant stereochemical control.
  3. Silylation of 3-phenylpropionitrile is achieved at the α-position with trimethylsilyl trifluoromethanesulfonate and trialkylamine base. Catalyzed by tetrabutylammonium ...


A Conservative Isoleucine To Leucine Mutation Of Klentaq1 Dna Polymerase 1 Induces Conformational Change For Cold-Sensitive Phenotype, Emma Caroline Materne Jan 2014

A Conservative Isoleucine To Leucine Mutation Of Klentaq1 Dna Polymerase 1 Induces Conformational Change For Cold-Sensitive Phenotype, Emma Caroline Materne

Honors Theses

Polymerase Chain Reaction (PCR) typically employs the Taq or Klentaq1 DNA polymerase from Thermus aquaticus to elongate short sequences of DNA during DNA amplification. Both Taq and Klentaq1 retain activity at room temperature. During assembly of PCR at room temperature, the activity of Taq and Klentaq1 can result in spurious products due to elongation of primers bound to non-target sequences. A mutation of isoleucine to leucine at position 707 of Klentaq1 results in slowing of the enzyme at room temperature without compromising the fidelity of the enzyme. To understand how a mutation over 20Å from the active site can affect ...


Formyl Group Activation Of Bromopyrrole Suzuki Cross-Coupling: Application To A Formal Synthesis Of Lamellarin G Trimethyl Ether, Andrew Harrison Jan 2014

Formyl Group Activation Of Bromopyrrole Suzuki Cross-Coupling: Application To A Formal Synthesis Of Lamellarin G Trimethyl Ether, Andrew Harrison

Honors Theses

Many biologically interesting compounds have been isolated from marine natural products, many of which contain characteristic pyrroles. Compounds such as polycitones, storniamides, ningalins, and lamellarins have been of particular interest for synthesis due to their vast pharmaceutical potential including the ability to fight tumors as well as induce cytolysis of drug resistant cancer cell lines. Previous studies on the synthesis of Lamellarin G trimethyl ether by the Gupton Group have relied upon vinylogous amide derivatives as building blocks.2 A new pathway utilizing a formylated pyrrole ring provides an interesting method for the synthesis of Lamellarin G trimethyl ether. Regioselective ...


Do The Inter-Nucleotide Domain Loops Act As An Entropic Sink In The Catalytic Activity Of 3-Phosphoglycerate Dehydrogenase (3pgdh)?, Cristina Adelia Meeham Jan 2014

Do The Inter-Nucleotide Domain Loops Act As An Entropic Sink In The Catalytic Activity Of 3-Phosphoglycerate Dehydrogenase (3pgdh)?, Cristina Adelia Meeham

Honors Theses

In protein science the relationship between protein dynamics and catalytic activity are the subject of considerable contemporary interest. Although protein motions are frequently observed during ligand binding and release steps, the contribution of protein motions to the catalysis of bond making/breaking processes is more difficult to probe and verify. Currently, the field of protein science is trying to uncover the deeper role that dynamics plays in the catalytic activity and allosteric regulation of proteins and to better understand how to more effectively and efficiently target proteins in cancer therapeutics and other metabolic pathways.


Trimethylsilyl Trifluoromethanesulfonate-Mediated Additions To Acetals, Nitrones, And Aminals, Chelsea Safran Apr 2013

Trimethylsilyl Trifluoromethanesulfonate-Mediated Additions To Acetals, Nitrones, And Aminals, Chelsea Safran

Honors Theses

One-pot reactions were studied in order to develop procedures for the formation of important carbon-carbon and carbon-nitrogen bonds that are easily reproducible. In the presence of trimethylsilyl triflouromethanesulfonate (TMSOTf), Mukaiyama-aldol and aldol-like reactions occur in one-pot due to TMSOTf acting as a Lewis acid and silylating agent. A variety of reactions, including methoxyalkylation, were performed to form carbon-nitrogen bonds. Here, research involving TMSOTf-mediated additions to acetals, nitrones, and aminals will be discussed.


Adenovirus Type 5 Virions Asymmetrically Lose Icosahedral Structure At Low Phs Of Endosomes, Jennifer Marie Jarboe Apr 2013

Adenovirus Type 5 Virions Asymmetrically Lose Icosahedral Structure At Low Phs Of Endosomes, Jennifer Marie Jarboe

Honors Theses

After receptor mediated endocytosis into an endosome, human Adenovirus Type 5 (Ad5) undergoes structural changes that allow the virus to release a viral protein, pVI, that lyses the endosome and releases the virus core into the cytosol, where it travels to the nucleus to insert its genome. Structural studies of Ad5 at a range of pHs typical of endosomes (7.5-4.5) using a transmission electron microscope show that Ad5 undergoes asymmetrical loss of proteins from vertex regions at the pH of the late endosome (pH5.15). Following further acidification, Ad5 ejects core material preferentially through one vertex—indicating an ...


The Inner Workings Of The Dna Copying Nanomachine : Kinetic Studies Of Dna Polymerase I From The Thermophilic Bacterium Rhodothermus Marinus, Emily P. Kornberg Apr 2013

The Inner Workings Of The Dna Copying Nanomachine : Kinetic Studies Of Dna Polymerase I From The Thermophilic Bacterium Rhodothermus Marinus, Emily P. Kornberg

Honors Theses

DNA polymerase I from Rhodothermus marinus is a high-fidelity DNA polymerase capable of operating at high temperatures and incorporating 2´,3´-dideoxynucleotides. The R. marinus DNA Polymerase I active site contains an unusual proline in the middle of a mobile “O helix.” This proline residue is hypothesized to decrease the relative free energy of a kinetic checkpoint termed the ajar conformation, and thereby slow the incorporation of incorrect nucleotides. We aim to test the accuracy of a newly developed nucleotide incorporation model, in which the enzyme allows the template to interact with the bound dNTP in the ajar conformation, whether ...


The Optimization Of A One-Pot Heteroconjugate Addition-Oxidation-Diels-Alder Reaction, Christina Vivelo Apr 2012

The Optimization Of A One-Pot Heteroconjugate Addition-Oxidation-Diels-Alder Reaction, Christina Vivelo

Honors Theses

Ynoate esters are ideal reagents for one-pot reactions due to their ability to undergo multiple addition reactions in one flask. Ethyl propiolate undergoes a heteroconjugate addition reaction with aromatic thiol nucleophiles, producing an enoate which is then oxidized by m-CPBA and is able to undergo a Diels–Alder reaction with cyclopentadiene. The work presents the optimization of a three-step heteroconjugate addition-oxidation-Diels–Alder reaction to yield cyclic compounds favoring endo stereochemistry, which may be used in further synthesis of biologically active compounds such as (+)-Methyl-5-epi-Shikimate or Deipeptyl-IV-Peptidase inhibitor.


Elucidation Of The Pax/Six Gene Regulatory Network In Ephydatia Muelleri, Anna Rued Apr 2012

Elucidation Of The Pax/Six Gene Regulatory Network In Ephydatia Muelleri, Anna Rued

Honors Theses

The evolution of gene regulatory networks accounts for much of the diversity we observe in the animal kingdom. In particular, the Pax/Six/Eya/Dac gene network has been known to play critical roles in development of all bilaterians and cnidarians. However, this network has not been characterized in Porifera. These studies focus on tracing the evolutionary history of the PSED network back to the most basal organism in the metazoan phylogeny through demonstrating the presence of a direct gene regulatory network between PaxB and Six1/2 orthologs in sponges. To this end, putatitve Six1/2 cis- regulatory elements were ...


The Relationship Between Live Coral And Macroalgae In South Caicos As Influenced By Herbivorous Fishes, Sarah Byce Apr 2012

The Relationship Between Live Coral And Macroalgae In South Caicos As Influenced By Herbivorous Fishes, Sarah Byce

Honors Theses

Marine life is the basis for most industries in the Turks and Caicos Islands, located on the outskirts of the Caribbean Sea. Few studies have been carried out to assess the current status of reefs in this region, especially those off the shore of South Caicos Island. The AGRRA v.4.0 methodologies were employed create baseline assessments of stony corals, macroalgae and associated fishes and to explore the relationships between these key reef organisms. This study was based on 10 different locations both inside and outside of Marine Protected Areas (MPAs) and including exposed and sheltered reefs in proximity ...


The Role Of Histidines In Neurosteroid Binding Of Nmda Glun2b And D Subunits, Sarah Rhoads Apr 2012

The Role Of Histidines In Neurosteroid Binding Of Nmda Glun2b And D Subunits, Sarah Rhoads

Honors Theses

Implicit in cellular mechanisms essential for learning and memory, NMDA receptors are heterotetrameric members of the family of ionotropic glutamate receptors. Activation of the glutamate-specific receptor subunits results in the opening of ion channels, triggering an excitatory pathway, which can be moderated by certain endogenous and exogenous compounds. Previous research with the endogenous neurosteroids pregnenolone sulfate (PS) and 3α-hydroxy-5-β-20-one sulfate (PregS) have indicated that the binding of these neurosteroids to NMDA receptors containing the four A-D isoforms of the GluN2 subunit affects current flow through them1. Binding of PS to NMDA receptors containing GluN2A or GluN2B subunits causes an increased ...


Determination Of The Atomic Resolution Structure Of A Dna Polymerase I Isolated From Rhodothermus Marinus, Natalie S. Omattage Apr 2012

Determination Of The Atomic Resolution Structure Of A Dna Polymerase I Isolated From Rhodothermus Marinus, Natalie S. Omattage

Honors Theses

DNA polymerase I employs a multistep mechanism for sorting correctly paired nucleotides from mismatches. We aim to characterize reaction intermediates during nucleotide selection to better understand how this class of enzymes achieves high DNA replication fidelity. DNA polymerase I from R. marinus contains an unusual and disruptive proline in the mobile O helix near the active site. To characterize this enzyme, the structure of the large (5´-to-3´ exo-deficient) fragment of the R. marinus DNA polymerase I (RF) was solved to 2.95 Å (R = 0.234) using multi-wavelength anomalous dispersion. Alignment with ...