Digital Commons Network^™

A Small Molecule That Binds And Inhibits The Etv1 Transcription Factor Oncoprotein, Marius C. Pop, Nicolas Stransky, Colin W. Garvie, Jean-Philippe Theurillat, Emily C. Hartman, Timothy A. Lewis, Cheng Zhong, Elizabeth K. Culyba, Fallon Lin, Douglas S. Daniels, Raymond Pagliarini, Lucienne Ronco, Angela N. Koehler, Levi A. Garraway

Chemistry Faculty Publications

Members of the ETS transcription factor family have been implicated in several cancers, where they are often dysregulated by genomic derangement. ETS variant 1 (ETV1) is an ETS factor gene that undergoes chromosomal translocation in prostate cancers and Ewing's sarcomas, amplification in melanomas, and lineage dysregulation in gastrointestinal stromal tumors. Pharmacologic perturbation of ETV1 would be appealing in these cancers; however, oncogenic transcription factors are often deemed “undruggable” by conventional methods. Here, we used small-molecule microarray (SMM) screens to identify and characterize drug-like compounds that modulate the biological function of ETV1. We identified the 1,3,5-triazine small molecule BRD32048 as a …

Determination Of The Factors That Affect The Gas-Phase Reactivity Of Metal-Centered Cyclopropanation Catalysts And Examination Of The Properties Of Their Reaction Products, Jamal Aldajaei

Theses and Dissertations

Gas phase studies of organometallic systems have provided deep insight into reaction mechanisms and reaction intermediates. In this thesis, several metal/ligand systems were examined in an effort to form metal carbenes in the gas phase. With cobalt and iron porphyrins, the carbene undergoes metal-ligand insertion. With copper bis-oxazolines, metal carbenes tend to undergo metal-ligand insertion and a Wolff rearrangement. To avoid insertions, we turned to a rigid ligand, 1, 10-phenanthroline. Under ESI conditions, a copper (I) complex with phenanthroline can be formed. When treated with diazoacetate esters, the dominant product results from addition with loss of nitrogen followed by loss …

Probing Stability And Unfolding Of The N-Terminal Domains 5-6 Of Wilson Protein, Ibtesam Y. Alja'afreh, Ramakrishna Guda, David L. Huffman

Research and Creative Activities Poster Day

The Wilson protein (ATP7B) is a copper transporting P1b type ATPase found in the liver, brain, and other organs. The N-terminal end consists of six copper binding domains which have a ferrodoxin βαββαβ fold with a CxxC motif. Despite similarities in copper binding affinities they interact differently with the HAH1 metallochaperone. Studying the stability of these domains will help understanding the differences in their functions. The stability of WLN5-6 was probed using several different methods: Dynamic light scattering (DLS), Circular dichroism (CD) and Fluorescence spectroscopy methods.

Previous studies show that WLN5-6 has a spherical shape and CD chemical unfolding studies …

Site-Specific Nitration Of Apolipoprotein A-I At Tyrosine 166 Is Both Abundant Within Human Atherosclerotic Plaque And Dysfunctional, Joseph A. Didonato, Kulwant Aulak, Ying Huang, Matthew A. Wagner, Gary Gerstenecker, Celalettin Topbas, Valentin Gogonea, Anthony J. Didonato, W.H. Wilson Tang, Ryan A. Mehl, Paul L. Fox, Edward F. Plow, Jonathan D. Smith, Edward A. Fisher, Stanley L. Hazen

Chemistry Faculty Publications

We reported previously that apolipoprotein A-I (apoA-I) is oxidatively modified in the artery wall at tyrosine 166 (Tyr166), serving as a preferred site for post-translational modification through nitration. Recent studies, however, question the extent and functional importance of apoA-I Tyr166 nitration based upon studies of HDL-like particles recovered from atherosclerotic lesions. We developed a monoclonal antibody (mAb 4G11.2) that recognizes, in both free and HDL-bound forms, apoA-I harboring a 3-nitrotyrosine at position 166 apoA-I (NO2-Tyr166-apoA-I) to investigate the presence, distribution, and function of this modified apoA-I form in atherosclerotic and normal artery wall. We also developed recombinant apoA-I with site-specific …

Synthesis And Purification Of The Glycosphingolipid Csa-13, Tyler Olsen, Dr. Paul Savage

Journal of Undergraduate Research

The need for novel antibiotic mechanisms is prevalent. Common antimicrobial medicines such as penicillin, ampicillin and vancomycin have started becoming obsolete as resistant strains of bacteria become more widespread. The main problem with antibiotics is the rapid mutations that bacteria undergo. Eventually one cell will develop resistance, and then have that mutation selected for as patients undergo antibiotic therapy. Bacteria are rapidly changing to combat the many new antibiotic variants that have come out.

Searching For Nascent Peptides That Cause Ribosome Stalling, Shankar Parajuli, Dr. Allen Buskirk

Journal of Undergraduate Research

Ribosomes are molecular machines that synthesize all the proteins for all living cells. Ribosomes sometimes stall and cannot complete the synthesis of a given protein. Some peptides interact with the ribosome during their own translation and induce stalling.1 The SecM and TnaC peptides in E. coli, for example, have been found to play a key regulatory role in translation of genes found on the same mRNA.2

Electrospray Of Bacteria Intact And Viable, Sara Pratt, Dr. Daniel Austin

Journal of Undergraduate Research

In this project we wanted to see if bacteria can survive a process called electrospray ionization (ESI). While bacteria survival of ESI has not previously been demonstrated, viruses survivability has1. The process of ESI consists of spraying a solution of the desired analyte in a strong electric field. Solution flowing through a capillary forms a Taylor cone at the end from which charged droplets emit. As solvent evaporates, the droplets break apart. As solvent continues to evaporate, that process is repeated and eventually forms individually charged particles once all the solvent is evaporated. The ESI in this experiment is done …

Bioactive Lipid Analysis Of Asthma-Induced Lung Tissue With A Focus On Biomarker Identification, Mackay Merrill, Dr. John Prince

Journal of Undergraduate Research

Initially, the goal of my project was to search for biologically active lipids in the lung tissue of mice with and without asthma (as opposed to those which simply form the membranes of cells) and determine if any of these lipids could serve as indicators of the disease. Over the course of experimentation, the focus shifted to these membrane (or structural) lipids. I planned to find indicative lipids (biomarkers) using mass spectrometry and statistical analysis.

Combination Of The Computational Methods: Molecular Dynamics, Homology Modeling And Docking To Design Novel Inhibitors And Study Structural Changes In Target Proteins For Current Diseases, Katherine Cristina Parra

USF Tampa Graduate Theses and Dissertations

In this thesis, molecular dynamics simulations, molecular docking, and homology modeling methods have been used in combination to design possible inhibitors as well as to study the structural changes and function of target proteins related to diseases that today are in the spotlight of drug discovery. The inwardly rectifying potassium (Kir) channels constitute the first target in this study; they are involved in cardiac problems. On the other hand, tensin, a promising target in cancer research, is the second target studied here.

The first chapter includes a brief update on computational methods and the current proposal of the combination of …

The Art And Science Of Living In The Present (Text And Video), Rebecca Roesner

Honorees for Teaching Excellence

No abstract provided.

Detection Of Heavy Transition Metal Cations Using Novel Chemosensors, Shannon Rhodes

Honors College Theses

Transition metals (TM) are found in the environment and living systems. When present in excess, these metals can trigger health problems, which include memory loss and cognitive functions. In this project, commercially-available compounds were used to aid in the making of novel mono- and di-triazole molecular sensors with a well-known reaction called “click chemistry”. These sensors were used efficiently and selectively to attract a specific metal like iron III, copper, and zinc. Six sensors were tested via UV-spectroscopy, NMR, and fluorescence with the cations and selectivity increased as the sensors were altered.

Photocatalysis And Grazing-Ion Beam Surface Modifications Of Planar Tio2 Model Systems, Timothy Luttrell

USF Tampa Graduate Theses and Dissertations

This dissertation is related to the understanding of catalytic reactions of metal oxides. For several decades, the surfaces and bulk of materials have been probed to determine additional properties that relate to photocatalytic applications. This investigation furthers these efforts by the (a) modification of a metal oxide surface to isolate known influences of chemical properties and (b) proposing and utilizing a novel methodology for attribution of photocatalytic activity to a discernable influence. For the first effort, by effectively utilizing a known technique for a new application on a metal oxide, such isolations can be made despite unfavorable states. For the …

In Vitro Activation Of Human Follicular Dentritic Cells And Its Effects On Human Immunodeficiency Virus Infection, Sean Llewellyn, Dr. Gregory F. Burton

Journal of Undergraduate Research

HIV is known to survive on follicular dendritic cells (FDCs) for many months and is believed to contribute to persisting HIV infection. FDCs protect HIV from degradation, thereby prolonging the infectivity of the virus. Moreover, when virus is trapped on FDCs, it escapes the ability of neutralizing antibodies (NtAb) to block infection of CD4+ T cells and subsequent removal of virus from the body. We postulate that FDC CD32 and/or CD21 contribute to maintaining virus infectivity and permitting infection in the presence of NtAb. Furthermore, when HIV forms an immune complex with antibodies and binds to CD32 and/or CD21, the …

Design & Synthesis Of Peptidomimetics Adopting Secondary Structures For Inhibition Of P53/Mdm2 Protein-Protein Interaction And Multiple Myeloma Cell Adhesion, Hyun Joo Kil

USF Tampa Graduate Theses and Dissertations

The protein-protein interactions (PPIs) occur when two or more proteins are bound together. Also, this protein-protein interactions (PPIs) cause the various biological processes in the body. Due to this reason, abilities of controlling or inhibiting PPIs can give us promising advantages like (1) better understanding of biological systems, (2) development of new diagnostic approaches for health or disease, and (3) establishment of novel molecular therapeutics. Many proteins adopt the secondary structures, where most of protein-protein interactions take place. -Helices and -sheets are the prevalent secondary conformations, but there are extended secondary structures such as -hairpins, -turns, 310 helix, and so …

Effects Of Oxidative Stress On J774 Macrophages, Katelyn Chessier

Senior Honors Projects

No abstract provided.

Case Study Of A Successful Educational Partnership: University Of Illinois At Urbana-Champaign And The Illinois Mathematics And Science Academy, Dave Devol

Faculty Publications & Research

This article describes partnerships between an NCSSSMST member institution and a research university and the use of student-generated survey data as a means of both professional self-reflection and asking further questions. As a chemist, I have been trained to write in the style of scientists, and in fact I teach a course at the Illinois Mathematics and Science Academy on the methods of science and scientific writing. This article is intentionally not written in a scientific style; rather is written to convey a story of how a partnership between institutions naturally progressed into my current area of research into motivational …

Designing Conical Intersections For Light-Driven Single Molecule Rotary Motors: From Precessional To Axial Motion, Michael Filatov, Massimo Olivucci

Chemistry Faculty Publications

In the past, the design of light-driven single molecule rotary motors has been mainly guided by the modification of their ground-state conformational properties. Further progress in this field is thus likely to be achieved through a detailed understanding of light-induced dynamics of the system and the ways of modulating it by introducing chemical modifications. In the present theoretical work, the analysis of model organic chromophores and synthesized rotary motors is used for rationalizing the effect of electron-withdrawing heteroatoms (such as a cationic nitrogen) on the topography and branching plane of mechanistically relevant conical intersections. Such an analysis reveals how the …

N-Methylmesoporphyrin Ix Fluorescence As A Reporter Of Strand Orientation In Guanine Quadruplexes, Navin C. Sabharwal , '14, V. Savikhin, Joshua R. Turek-Herman , '16, John Michael Nicoludis , '12, V. A. Szalai, Liliya A. Yatsunyk

Chemistry & Biochemistry Faculty Works

Guanine quadruplexes (GQ) are four-stranded DNA structures formed by guanine-rich DNA sequences. The formation of GQs inhibits cancer cell growth, although the detection of GQs invivo has proven difficult, in part because of their structural diversity. The development of GQ-selective fluorescent reporters would enhance our ability to quantify the number and location of GQs, ultimately advancing biological studies of quadruplex relevance and function. N-methylmesoporphyrin IX (NMM) interacts selectively with parallel-stranded GQs; in addition, its fluorescence is sensitive to the presence of DNA, making this ligand a possible candidate for a quadruplex probe. In the present study, we investigated the effect …

The Determination Of Mercury Levels In Aquatic Avian Populations Using Atomic Spectroscopy Techniques, Peter M. Klaeser

All Capstone Projects

Mercury contamination has been shown to have a negative impact in fish-eating birds, including impacts on behavior, reproductive success, and their overall survival. Higher than normal mercury levels have been detected in birds who depend on fish for their food. High levels of mercury have been detected in the bird’s blood and feathers using analytical techniques. The present accepted method of determining levels of mercury in feathers and blood is the use of atomic spectroscopy. The amount of mercury in feathers appears to depend on the growth of the feathers with more growth associated with lower levels of mercury contamination. …

The Roles Of Phosducin-Like Protein 1 And Programmed Cell Death Protein 5 As Molecular Co-Chaperones Of The Cytosolic Chaperonin Complex, Christopher M. Tracy

Theses and Dissertations

A fundamental question in biology is how proteins, which are synthesized by the ribosome as a linear sequence of amino acids, fold into their native functional state. Many proteins require the assistance of molecular chaperones to maneuver through the folding process to protect them from aggregation and to help them reach their native state in the very concentrated protein environment of the cell. This study focuses on the roles of Phosducin-like Protein 1 (PhLP1) and Programmed Cell Death Protein 5 (PDCD5) as molecular co-chaperones of the Cytosolic Chaperonin Complex (CCT).Signaling in retinal photoreceptors is mediated by canonical G protein pathways. …

Reactivity Studies Of Tridhydropyridine Radical Cautions By Using Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry And Advancement Of Mass Spectrometric Analysis Of Asphaltenes And Degradation Products, Mohammad Sabir Aqueel

Open Access Dissertations

Aromatic organic molecules which have unpaired electrons play an important role in a variety of applications in the fields of organic synthesis, organic magnets, and biological activity of organic compounds. Several studies have been published on σ- type carbon-centered mono- and biradicals. Reactive intermediates with three formally unpaired electrons are known as triradicals. They can be defined as species with three electrons distributed in three degenerate or nearly degenerate orbitals, based on Salem's definition of biradicals from the electronic structure point of view. Very little is known about the reactivity of carbon-centered σ,σ,σ- triradicals due to the complexity of studying …

Photoreactions Of A Water Soluble Poly-Isoquinolpyrrole With Plasmid Dna, Gregory Versteeg

Honors Theses

With the goal of creating a porphyrin we reacted isoquinol pyrrole, p-fluorobenzaldehyde, and boron trifluoride etherate under appropriate conditions. Instead of a porphyrin being synthesized, we created polyisoquinol pyrrole in high yield and with great absorption properties around 600nm. We characterized this compound via UV/vis spectroscopy, proton NMR, and electrochemistry. The compound was then reacted with [Ru(bipy)2Cl2] to create a cationic compound and this molecule was tested as a possible photosensitizer for photodynamic therapy (PDT) but it was unable to photocleave plasmid DNA above 550nm. The original compound was then methylated and this new compound was also tested as a …

Section Abstracts: Chemistry

Virginia Journal of Science

Abstracts of the Chemistry Section for the 92nd Annual Meeting of the Virginia Academy of Science, May 13-15, 2014, Virginia Commonwealth University, Richmond, Virginia

Size-Dependent Interactions Of Metal Nanoparticles With Fluorophores And Semiconductors, Liyana A. Wajira Ariyadasa

Dissertations

In recent years, nanoscale metallic particles have gained considerable interest due to their potential applications in advanced technology. Despite such interest, synthetic procedures that produce gram-scale, well-defined metallic nanoparticles with controlled size and shape, especially with diameters less than 5 nm remains a challenge. Our work has focused on developing synthetic procedures that produce well-defined platinum and palladium metal nanoparticles in the 1-5 nm size range. Thioether ligands were used as stabilizers and resulted in metal nanoparticles with controlled size. The nanoparticles were characterized using transmission electron microscopy (TEM), x-ray diffraction (XRD), selected area electron diffraction (SAED), x-ray photoelectron spectroscopy …

A Meta Analysis Of Pancreatic Microarray Datasets Yields New Targets As Cancer Genes And Biomarkers, Nalin C. W. Goonesekere, Xiaosheng Wang, Lindsey Ludwig, Chittibabu Guda

Faculty Work

The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a five year survival rate of less than 5%. Improved screening for earlier diagnosis, through the detection of diagnostic and prognostic biomarkers provides the best hope of increasing the rate of curatively resectable carcinomas. Though many serum markers have been reported to be elevated in patients with PC, so far, most of these markers have not been implemented into clinical routine due to low sensitivity or specificity. In this study, …

Sdsl-Epr Structural Studies Of The Cytoplasmic Helix In Novel Full-Length Constructs Of The Influenza A M2 Protein, Megan E. Thompson , '14

Senior Theses, Projects, and Awards

The M2 protein of the influenza A virus is a homotetrameric transmembrane proton channel implicated in several stages of the viral replication process. Each of its 97-residue monomers is known to include a transmembrane α-helix. but the structures of the N- and C-terminal domains have not yet been solved. A significant barrier to an atomic level understanding of the M2 protein is the difficulty associated with expression and purification of the full-length protein, which has primarily been studied in the form of truncated constructs covering the amphipathic helix and a short C-terminal segment. This C-terminal segment, which includes residues 46-62, …

Classifying The Functionality Of Primosome Protein A In Deinococcus Radiodurans, Jacob Boone

Honors Theses

Deinococcus radiodurans is an extremophile bacterium with the capacity to withstand tremendous DNA damage that causes disruption of replisome complex activity. The efficiency of origin-independent replisome reloading directly correlates to effectiveness of DNA damage coping strategies, and remains largely undefined in D. rad primosome components. Investigation of D. rad PriA as a helicase protein was conducted to determine if PriA could be classified as a fossilized helicase. This project tested the three functions of known helicases by comparing E. coli and D. rad PriA. DNA binding, DNA unwinding, and ATP hydrolysis assays were performed on both proteins separately and results …

Synthesis, Characterization And Potential Applications Of Palladium And Ruthenium Nanostructures, Clara Patrice Adams

Dissertations

Controlling the size and shape of metal nanostructures is important for tuning the intrinsic chemical and physical properties of materials, and consequently their potential technological applications. Modulating the morphology of metal nanostructures is essential to understanding the structure-function relationship (for example, optical, magnetic, catalytic, and electronic properties) under various environmental conditions. Our work describes the development of new procedures for the synthesis of well-defined isotropic and anisotropic nanoparticles consisting of palladium (Pd) and ruthenium (Ru). Characterization of the nanostructures was carried out using transmission electron microscopy (TEM), high resolution-TEM (HRTEM), powder x-ray diffraction (XRD), selected area electron diffraction (SAED) and …

Fundamental Studies Of Protein Ionization For Improved Analysis By Electrospray Ionization Mass Spectrometry And Related Methods, Kevin A. Douglass

Dissertations

Mass spectrometry (MS) is an analytical technique in which a sample is converted to gas-phase ions that are subsequently separated and detected. It offers great speed, selectivity, and sensitivity during analysis, characteristics which have enabled it to become a leading method for the study of proteins. The applications of MS for these biologically significant macromolecules range from accurately determining identity and sequence to shedding light on post-translational modifications and protein-molecule interactions. As a first step towards analysis by MS, gas-phase protein ions must be formed. A common method for ionization is electrospray ionization (ESI), where a liquid sample including the …

Characterizing The Interactions Between Influenza A M2 Protein And Cholesterol In Membranes, Matthew R. Elkins , '14

Senior Theses, Projects, and Awards

The influenza A M2 protein is 97-residues in length and homotetramerizes to form a proton channel across the viral membrane early in the influenza life cycle. M2 is also implicated in the formation and budding of new viral particles in a process proposed to require membrane cholesterol. A potential cholesterol recognition amino acid consensus (CRAC) immediately C-terminal to the M2 transmembrane domain is thought to mediate the M2-cholesterol interaction. However, the finer details of this interaction are largely unknown. Using site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) spectroscopy, this research aims to gain a more detailed understanding of …