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Microwave-Assisted Synthesis Of Quinoxaline Derivatives, Eric Horsting Apr 2022

Microwave-Assisted Synthesis Of Quinoxaline Derivatives, Eric Horsting

Honors Theses

Quinoxaline and its derivatives have been studied extensively for their relevant biological activity and transition metal selectivity. These compounds are commonly used for their antimicrobial, antifungal, antiparasitic activity, and relevance in the treatment of metabolic diseases [6]. More recently, quinoxaline’s ability to inhibit gram-positive bacterial growth has been found especially in oxygen- containing compounds, yielding promising candidates to prevent cancerous tumor growth [5]. The breadth of quinoxaline makes it a valuable tool within the research community However, its synthesis requires complex solvents, extended reaction times, and often produces a low yield. By using a microwave-assisted synthesis, this novel methodology offers …


Understanding The Hydrolytic Activity Of Papiliotrema Laurentii On Polyester Polyurethane Coatings, Ariana L. Santos Apr 2022

Understanding The Hydrolytic Activity Of Papiliotrema Laurentii On Polyester Polyurethane Coatings, Ariana L. Santos

Honors Theses

Though plastic polymers such as polyester polyurethanes have many applications from electronics to aircraft coatings, their resistance to natural degradation presents an environmental concern. Therefore, elucidating the mechanism of degradation from microorganisms that were discovered breaking down the coating of a cargo aircraft may offer insights into a method of bioremediation. To explore this, the fungus Papiliotrema laurentii (one microorganism isolated from the consortium) was cultured in several different media types at different pH levels in order to understand how it adjusts its protein secretion patterns to environmental changes. 2D gel electrophoresis, isoelectric focusing (IEF) and a variety of gel …


Isolating And Manipulating Microorganisms Using Ureolysis For Creating Extraterrestrial Microbial Biotechnology Systems, Nina M. Wendel May 2021

Isolating And Manipulating Microorganisms Using Ureolysis For Creating Extraterrestrial Microbial Biotechnology Systems, Nina M. Wendel

Honors Theses

The conversion of CO2 into valuable feedstocks, such as high energy sugars would create paradigm shifting technologies for applications on earth and for interplanetary exploration. Microbes and microbe consortia may be one way to accomplish this conversion. Approximately 70% of the Earth’s microorganisms live in the dark marine biosphere (DMB). The DMB, which covers more than two-thirds of the Earth, is known as the most isolated region of the Earth’s largest CO2 sink. Despite its role in reducing CO2 and its vast majority of microorganisms, only about 5% of the sea floor has been explored. Due to the limited knowledge …


Development Of Nucleic Acid Aptamers To Inhibit Bacterial Efflux Pumps, Emilie A. Moses May 2021

Development Of Nucleic Acid Aptamers To Inhibit Bacterial Efflux Pumps, Emilie A. Moses

Honors Theses

Multidrug resistance in bacteria, defined as the ability of a bacterial strain to resist the killing effects of more than one antibiotic, represents a major threat to global healthcare. Every year in the United States, two million people are infected with a multidrug resistant strain of bacteria. According to the Center for Disease Control (CDC), out of those two million people, about 35,000 will die from their infection. Thus, these multidrug resistant diseases are considered by the CDC to be the most dangerous diseases in the world. While multidrug resistance can occur through several different mechanisms, a major contributor to …


The Tolerance Of Shewanella Woodyi For Electric Potentials And Heavy Metals As Biofilms, Christopher Thomas Mortensen Dec 2020

The Tolerance Of Shewanella Woodyi For Electric Potentials And Heavy Metals As Biofilms, Christopher Thomas Mortensen

Honors Theses

Shewanella woodyi is a bioluminescent marine organism that is known to be metal tolerant and modulate the intensity of its luminescence with electrochemical potential. The viability of S. woodyi as a bioreporter for the toxic heavy metal zinc, copper, and silver was analyzed. Biofilms of S. woodyi was grown on marine broth agar plates and then exposed to various concentrations of each metal ion to evaluate biofilm response to the metal ions that were generated from an operating short circuited electrode containing either Zn, Cu, or Ag metal. The ability of the bacteria to tolerate the heavy metals and continue …


Quantitative Trait Loci (Qtl) Underlying Phenotypic Variation In Bioethanol-Related Processes In Neurospora Crassa, Joshua C. Waters, Deval Jhaveri, Justin C. Biffinger, Kwangwon Lee Feb 2020

Quantitative Trait Loci (Qtl) Underlying Phenotypic Variation In Bioethanol-Related Processes In Neurospora Crassa, Joshua C. Waters, Deval Jhaveri, Justin C. Biffinger, Kwangwon Lee

Chemistry Faculty Publications

Bioethanol production from lignocellulosic biomass has received increasing attention over the past decade. Many attempts have been made to reduce the cost of bioethanol produc- tion by combining the separate steps of the process into a single-step process known as consolidated bioprocessing. This requires identification of organisms that can efficiently decompose lignocellulose to simple sugars and ferment the pentose and hexose sugars lib- erated to ethanol. There have been many attempts in engineering laboratory strains by add- ing new genes or modifying genes to expand the capacity of an industrial microorganism. There has been less attention in improving bioethanol-related processes …


Identifying Natural Inhibitors Of Bacterial Efflux Pumps, Marrisa Therriault Apr 2019

Identifying Natural Inhibitors Of Bacterial Efflux Pumps, Marrisa Therriault

Honors Theses

Antibiotic resistance is a constantly progressing epidemic. Many strains of bacteria have developed a resistance to antibiotics, resulting in prolonged sickness and death. Resistance can be to a specific drug (single drug resistance) or to multiple drugs (multi-drug resistance). This resistance can be caused by a tripartite protein pump called an efflux pump that extends through the inner and outer membranes of the bacterium to pump antibiotics from the inside of the cell to the extracellular environment. In E. coli the efflux pump is called AcrAB-TolC. In the efforts to combat this problem, this experiment focuses on the inactivation of …


Tracking Disparate Colony Morphological Trends With Thermus Scotoductus, Matthew P. Leverick Apr 2019

Tracking Disparate Colony Morphological Trends With Thermus Scotoductus, Matthew P. Leverick

Honors Theses

When plating most mesophilic bacteria, the colony shape, size, and color tends to be uniform when a single strain is present. When plating defined cell densities of T. scotoductus, however, the colonies were not of uniform size and shape while it grew on the surface. In this project, we sought to observe trends in colony morphology (shape and size) changes using the thermophile Thermus scotoductus on nutrient rich agar plates at 60°C. A general planktonic growth curve was also created to help characterize the activity of this bacterium. This project was our first attempt to characterize if this unusual phenomenon …


Analysis And Review Of The Effects Of Bacterial Competition On Efflux Pump Inhibition, Robert Leszcynski Apr 2019

Analysis And Review Of The Effects Of Bacterial Competition On Efflux Pump Inhibition, Robert Leszcynski

Honors Theses

Multidrug resistant antibacterial strains are a dangerous problem for modern medical professionals. When cells of two different strains are grown together, they must compete with each other for nutrients. This competition can lead to the production of harmful compounds that are toxic to the competing strain. One such compound may be a compound that inhibits the efflux of antibiotics from the cell. When the cells compete with one another, one or both of the cells will produce compounds that are harmful to the competing strain.


Boron Dipyrromethenes: Synthesis And Computational Analysis, Eduardo Rivé Lockwood Apr 2019

Boron Dipyrromethenes: Synthesis And Computational Analysis, Eduardo Rivé Lockwood

Honors Theses

Recently, there has been a growing interest in the boron dipyrromethene (BODIPY, 4,4′- difluoro-4-bora-3a,4a-diaza-s-indacene) compounds. BODIPY compounds have fascinating properties that allow for the absorption and emission of light in the near infrared region of the electromagnetic spectrum. These molecules are highly modifiable making them ideal chemicals for the use of photoelectric energy conversion such as for commercial use in dye sensitized solar cells (DSSCs). It has been previously shown that different meso compounds have only a slight effect on the absorptive capabilities of these BODIPY compounds. We believe that the BODIPY compounds’ lack of planarity is one of the …


The Impact Of The 515nm Effect On 1o2 Quenching In Photosynthesis: Model System Studies Using Β-Carotene–Acid Complexes, Lauren A. Hoody Apr 2018

The Impact Of The 515nm Effect On 1o2 Quenching In Photosynthesis: Model System Studies Using Β-Carotene–Acid Complexes, Lauren A. Hoody

Honors Theses

β-carotene (βC) is an orange pigment present in the photosynthetic reaction center (PRC) of green plants, where it plays a vital role in photosynthesis: It quenches singlet oxygen (1O2 , a toxic oxidizing species generated during photosynthesis) before the 1O2 damages chlorophyll and other components of the PRCs. During photosynthesis, βC temporarily converts from its native orange–450 state to a pink–515 state via the so–called 515nm Effect. Because of the differences between the electronic structures of orange–450 and pink–515, I hypothesize that pink–515 will quench 1O2 less efficiently than orange–450. This hypothesis has not been tested to date because orange–450 …


Eigenstate–Specific Temperatures In Two–Level Paramagnetic Spin Lattices, Mark Masthay, Calley N. Eads, Amber N. Johnson, R. Gerald Keil, Phillip Miller, Ross E. Jones, Joe D. Mashburn, Harry B. Fannin Dec 2017

Eigenstate–Specific Temperatures In Two–Level Paramagnetic Spin Lattices, Mark Masthay, Calley N. Eads, Amber N. Johnson, R. Gerald Keil, Phillip Miller, Ross E. Jones, Joe D. Mashburn, Harry B. Fannin

Chemistry Faculty Publications

Increasing interest in the thermodynamics of small and/or isolated systems, in combination with recent observations of negative temperatures of atoms in ultracold optical lattices, has stimulated the need for estimating the conventional, canonical temperature Tconvc of systems in equilibrium with heat baths using eigenstate-specific temperatures (ESTs). Four distinct ESTs—continuous canonical, discrete canonical, continuous microcanonical, and discrete microcanonical—are accordingly derived for two-level paramagnetic spin lattices (PSLs) in external magnetic fields. At large N, the four ESTs are intensive, equal to Tconvc, and obey all four laws of thermodynamics. In contrast, for N < 1000, the ESTs of most PSL eigenstates are non-intensive, differ from Tconvc, and violate each of the thermodynamic laws. Hence, in spite of their similarities to Tconvc at large N, the ESTs …


The Autophagy-Related Beclin-1 Protein Requires The Coiled-Coil And Bara Domains To Form A Homodimer With Submicromolar Affinity, Matthew J. Ranaghan, Michael A. Durney, Michael F. Mesleh, Patrick R. Mccarren, Colin W. Garvie, Douglas S. Daniels, Kimberly L. Carey, Adam P. Skepner, Beth Levine, Jose R. Perez Nov 2017

The Autophagy-Related Beclin-1 Protein Requires The Coiled-Coil And Bara Domains To Form A Homodimer With Submicromolar Affinity, Matthew J. Ranaghan, Michael A. Durney, Michael F. Mesleh, Patrick R. Mccarren, Colin W. Garvie, Douglas S. Daniels, Kimberly L. Carey, Adam P. Skepner, Beth Levine, Jose R. Perez

Chemistry Faculty Publications

Beclin-1 (BECN1) is an essential component of macroautophagy. This process is a highly conserved survival mechanism that recycles damaged cellular components or pathogens by encasing them in a bilayer vesicle that fuses with a lysosome to allow degradation of the vesicular contents. Mutations or altered expression profiles of BECN1 have been linked to various cancers and neurodegenerative diseases. Viruses, including HIV and herpes simplex virus 1 (HSV-1), are also known to specifically target BECN1 as a means of evading host defense mechanisms. Autophagy is regulated by the interaction between BECN1 and Bcl-2, a pro-survival protein in the apoptotic pathway that …


The Effects Of Structural Modification Of The Wing Helix Domain Of Pria On Bacterial Dna, Erich Auer Apr 2017

The Effects Of Structural Modification Of The Wing Helix Domain Of Pria On Bacterial Dna, Erich Auer

Honors Theses

During a cell’s life it must copy itself or face death. For the cell to form a new copy it must replicate its DNA, this DNA is the blueprint for the essential components of the cell. The replication process does not always go to completion, which is necessary for the cell to survive, so there are mechanisms to keep the replication process running smoothly. In bacteria, PriA is used to restart replication after damage to the DNA. By looking at the structure of PriA we can start to determine how exactly it works with the damaged DNA and restart the …


Preparation, Analysis And Derivatization Of Benzotris(Thiazole) Triamine, Jonathan Patrick Peter Alessi Apr 2017

Preparation, Analysis And Derivatization Of Benzotris(Thiazole) Triamine, Jonathan Patrick Peter Alessi

Honors Theses

Multiple fields are areas of active research where organic materials hold considerable promise, such as thermoelectrics or photovoltaics. In an effort to design and prepare a new system which would exhibit a set of promising features such as high thermal stability, high degree of planarity, rigid skeleton and strong electron accepting properties, we have undertaken the preparation and characterization of benzotrithiazole and its derivatives. Our work has led to a reproducible and scalable protocol for the generation of one particular structure: benzo[1,2-d:3,4-d':5,6-d"]tris(thiazole)-2,5,8-triamine. We have also conducted further attempts to functionalize this structure, leading to other derivatives of the target compound.


Synthesis Of Bis(Quinoxalino) Ligand For The Removal Of Transition Metal Contamination, Alexander J. Farmer Apr 2017

Synthesis Of Bis(Quinoxalino) Ligand For The Removal Of Transition Metal Contamination, Alexander J. Farmer

Honors Theses

Transition metal contamination is a constant concern both in the environment and in chemical reaction mixtures. One proposed solution, is the use of peraza-crown macrocycles to selectively bind and remove transition metals. The aim of our project is to determine the novel synthesis of bis(quinoxalino) peraza-crown macrocycles for use as ligands to bind to transition metals. Our proposed molecules incorporate the rigid quinoxaline subunit into an aza-crown macrocycle which can improve binding properties. The synthesis route is novel and overcomes several limitations of the existing methods of aza-crown macrocycle preparation. We have designed the synthesis in such a way that …


The Tribology And Chemistry Of Phosphorus Containing Lubricant Additives, David W. Johnson Oct 2016

The Tribology And Chemistry Of Phosphorus Containing Lubricant Additives, David W. Johnson

Chemistry Faculty Publications

Phosphate esters, thiophosphate esters and metal thiophosphates have been used as lubricant additives for over 50 years. Recently, phosphorus‐containing ionic liquids have emerged as a new class of lubricant additives. While the use of phosphorus compounds has been extensive, a detailed knowledge of how they work has been a much more recent development. In this chapter, the use of phosphate esters, thiophosphate esters, metal thiophosphates and phosphorus‐containing ionic liquids as antiwear or extreme pressure additives is discussed. The primary emphasis will be on how they form a protective film, which is both durable and reduces friction. The first part of …


Lubricants For Turbine Engines, David W. Johnson Sep 2016

Lubricants For Turbine Engines, David W. Johnson

Chemistry Faculty Publications

The lubricant systems used in turbine engine applications are discussed with respect to the particular problems associated with aircraft applications. After initially describing the relevant specifications, the typical basestocks are described along with some common degradation schemes. The additive systems, including antioxidants, anti-foaming agents, and anti-wear additives needed to achieve the typical specifications, are described along with their mechanism of action and degradation mechanisms. The methods used for the monitoring of lubricant health, including in-line and offline methods, are also discussed. Finally, future changes in specifications, basestocks, and additives are discussed with respect to new, high-performance bearing materials.


Synthesis And Flammability Testing Of Epoxy Functionalized Phosphorous-Based Flame Retardants, Vladimir Benin, Xuemei Cui, Alexander Morgan, Karl Seiwert Aug 2015

Synthesis And Flammability Testing Of Epoxy Functionalized Phosphorous-Based Flame Retardants, Vladimir Benin, Xuemei Cui, Alexander Morgan, Karl Seiwert

Chemistry Faculty Publications

Several potential new phosphorus-containing flame retardant molecules were evaluated for heat release reduction potential by incorporation of the molecules into a polyurethane, generated from methylene diphenyl diisocyanate and 1,3-propane diol. The heat release reduction potential of these substances was evaluated using the pyrolysis combustion flow calorimeter (PCFC). The polyurethanes were prepared in the presence of the potential flame retardants via solvent mixing and copolymerization methods to qualitatively evaluate their potential reactivity into the polyurethane prior to heat release testing. The functionality of the flame retardants was epoxide based that would potentially react with the diol during polyurethane synthesis. Flammability testing …


A Maltose-Binding Protein Fusion Construct Yields A Robust Crystallography Platform For Mcl1, Matthew C. Clifton, David M. Dranow, Alison Leed, Ben Fulroth, James W. Fairman, Jan Abendroth, Kateri A. Atkins, Ellen Wallace, Dazhong Fan, Guoping Xu, Z. J. Ni, Douglas S. Daniels, John Van Drie, Guo Wei, Alex B. Burgin, Todd R. Golub, Brian K. Hubbard, Michael H. Serrano-Wu Apr 2015

A Maltose-Binding Protein Fusion Construct Yields A Robust Crystallography Platform For Mcl1, Matthew C. Clifton, David M. Dranow, Alison Leed, Ben Fulroth, James W. Fairman, Jan Abendroth, Kateri A. Atkins, Ellen Wallace, Dazhong Fan, Guoping Xu, Z. J. Ni, Douglas S. Daniels, John Van Drie, Guo Wei, Alex B. Burgin, Todd R. Golub, Brian K. Hubbard, Michael H. Serrano-Wu

Chemistry Faculty Publications

Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligand-bound structures. The ability to obtain fragment-bound structures advances structure-based drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors.


Synthesis Of Phosphorus-Based Hemiacetals For Potential Flame Retardants, Sara Alakkad Apr 2015

Synthesis Of Phosphorus-Based Hemiacetals For Potential Flame Retardants, Sara Alakkad

Honors Theses

Flame retardants which contain a phosphorus moiety attached to a carbohydrate backbone were developed. To synthesize the flame retardants, carbohydrates and polyols were used as the starting materials which occur in nature and are environmentally and toxicologically safe materials. The two target structures include one with a triose substructure and one with a pentose substructure. For both situations, however, multiple steps were taken for the synthesis of the flame retardant, as the carbohydrate needed to be generated into its protected form. The protected carbohydrate then interacted with a dialkyl phosphite, resulting in a phosphorous hemiacetal. This hemiacetal was then deprotected …


Exploration Of Protein-Protein Interactions Involving Deinococcus Radiodurans Pria, Dnab And Ssb, Christopher S. Morrow Apr 2015

Exploration Of Protein-Protein Interactions Involving Deinococcus Radiodurans Pria, Dnab And Ssb, Christopher S. Morrow

Honors Theses

Deinococcus radiodurans is a species of bacteria that has sparked a lot of interest since its discovery due to its incredible resistance to ionizing radiation. When exposed to ionizing radiation the genome of D. radiodurans will sustain over one hundred double stranded breaks. D. radiodurans demonstrates the ability to repair its genome and restart replication after sustaining, typically lethal, DNA damage. This project examined the mechanism of replication restart in D. radiodurans by investigating primosome protein PriA interacting with replicative helicase DnaB and single stranded binding protein. Many different types of gel electrophoresis were employed to investigate potential protein complex …


Synthesis Of Potential Phosphorus-Nitrogen Containing Flame Retardants, Colin Kloock Apr 2015

Synthesis Of Potential Phosphorus-Nitrogen Containing Flame Retardants, Colin Kloock

Honors Theses

Production of extremely efficient flame retardants is ideal because, in many instances, the amount of flame retardants that are added to pre-production to the mixture are so large that they can have an effect on the physical properties of the material. In addition, these types of polymers, when added during production, are homogenously mixed throughout the mixture which means not only uniform distribution and therefore function, but a less concentration of the retardants need to be used. Using Phosphorus-Nitrogen containing flame retardants in mixtures can have two means by which they function. First is the ability of P-N compounds to …


Kinetic Characterization Of B-Carotene In N-Hexane At Various Oxygen Concentrations, Katelyn Mary Arnold Apr 2015

Kinetic Characterization Of B-Carotene In N-Hexane At Various Oxygen Concentrations, Katelyn Mary Arnold

Honors Theses

We have characterized the photo – degradation of ẞC in oxygenated and deoxygenated n–hexane solvent and in the solid phase using broadband (BB; λ ≥ 200 nm) and 313 nm filtered output of a 100 W Hg Arc lamp. Oxygen concentrations of 0, 10, 20, and 100% were used in the solution phase studies. ẞC(s) did not photo – degrade upon exposure to BB light under air atmospheres; the mass and appearance of the samples, TLC chromatograms, and the absorption spectra were all identical pre- and post-irradiation. In the solution phase, the order of the photo – degradation with respect …


Discovery Of Thienoquinolone Derivatives As Selective And Atp Non-Competitive Cdk5/P25 Inhibitors By Structure-Based Virtual Screening, Arindam Chatterjee, Stephen J. Cutler, Robert J. Doerksen, Ikhlas A. Khan, John S. Williamson Nov 2014

Discovery Of Thienoquinolone Derivatives As Selective And Atp Non-Competitive Cdk5/P25 Inhibitors By Structure-Based Virtual Screening, Arindam Chatterjee, Stephen J. Cutler, Robert J. Doerksen, Ikhlas A. Khan, John S. Williamson

Office for Research Publications and Presentations

Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer’s disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[3,2- …


Heat Release Of Polyurethanes Containing Potential Flame Retardants Based On Boron And Phosphorus Chemistries, Vladimir Benin, Bastien Gardelle, Alexander Morgan Aug 2014

Heat Release Of Polyurethanes Containing Potential Flame Retardants Based On Boron And Phosphorus Chemistries, Vladimir Benin, Bastien Gardelle, Alexander Morgan

Chemistry Faculty Publications

Using a polyurethane of methylene diphenyl isocyanate and 1,3-propane diol, several new non-halogenated aromatic boron and phosphorus flame retardants were evaluated for heat release reduction potential using the pyrolysis combustion flow calorimeter (PCFC). The polyurethanes were prepared in the presence of the potential flame retardants via solvent mixing and copolymerization methods, and were then analyzed via spectroscopic methods to determine if the flame retardant was still present in the final product. PCFC testing on the resulting products showed that the flame retardant molecule can have different effects on heat release depending upon how it is mixed into the polyurethane. Some …


Determination Of Corrosion Inhibitor Lubricity Improver In Jet Fuel By Liquid Chromatography-Electrospray Ionization Mass Spectrometry, David W. Johnson, Milissa Flake, Ryan Adams Jul 2014

Determination Of Corrosion Inhibitor Lubricity Improver In Jet Fuel By Liquid Chromatography-Electrospray Ionization Mass Spectrometry, David W. Johnson, Milissa Flake, Ryan Adams

Chemistry Faculty Publications

Military jet fuel (JP-8) is very similar to commercial jet fuel (Jet A) except for the presence of three additives, fuel system icing inhibitor, corrosion inhibitor–lubricity improver (CI-LI), and antistatic additive, which are added to improve characteristics of JP-8. Of particular interest is the CI-LI additive; the most common active ingredient is a dimer of linoleic acid. This article focuses on quantification of the active ingredient in the CI-LI additive by liquid chromatography–mass spectrometry (LC–MS). This method will allow the determination of CI-LI content in military jet fuel samples.


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 Apr 2014

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 …


Investigating Bacterial Replication Restart: Can D.Rad Pria Load D.Rad Dnab Onto Dna Forks With A Leading Strand Gap?, Michael Ryan Apr 2014

Investigating Bacterial Replication Restart: Can D.Rad Pria Load D.Rad Dnab Onto Dna Forks With A Leading Strand Gap?, Michael Ryan

Honors Theses

The bacteria Deinococcus radiodurans (D. rad) is able to survive multiple double stranded breaks to its DNA with no detriment to its health as its genome can be fully repaired in a matter of hours. During bacterial DNA replication, points of DNA damage can cause replication to cease, requiring an origin independent replisome loading pathway to resume the replication. This pathway is called replication restart , a highly conserved pathway in bacteria. In the E. coli replication restart pathway primosome proteins function by binding to the DNA fork and facilitating the loading of the DnaB helicase onto the replication fork. …


Synthesis And Characterization Of A Tetra-Ruthenated Naphthylbiliverdin, Ashley M. Berding Apr 2014

Synthesis And Characterization Of A Tetra-Ruthenated Naphthylbiliverdin, Ashley M. Berding

Honors Theses

A new naphtylbiliverdin compound has been synthesized which offers intense absorption with the photodynamic therapy window (600 nm – 850 nm). The compound has been characterized by proton NMR, high resolution electrospray mass spectrometry, elemental analysis, and UV/vis spectroscopy. Coordination of four ruthenium(II) polypyridyl complexes was accomplished by standard procedures. The new tetra-ruthenated naphthylbiliverdin was characterized by elemental analysis. Cyclic voltammetry measurements reveal that all four ruthenium moieties are coordinated to the pyridyl groups of the biliverdin compound. The intense metal to ligand charge transfer (MLCT) bands of the peripheral ruthenium groups overshadow the absorption due to the biliverdin compound; …