Weekly: ILC 118 – 1:30 pm to 2:20 pm
Friday, May 3, 2019
Tyler Gilbert, Cornell Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “5’-methylthioadenosine Nucleosidase as a Target for Antiparasitic Drug Development”
Giardia intestinalis is the most frequently reported intestinal protozoan infection with an estimated 200 million cases per year in Africa, Asia and Latin America, with one to two million cases in the United States. Entamoeba histolytica is a potent pathogenic parasite responsible for several tens of thousands of deaths per year as a consequence of severe infections that cause fulminating colitis or liver abscess. Giardiasis and amoebiasis are currently treated with metronidazole, a reasonably anticipated human carcinogen. Isolates of both parasites have been discovered that demonstrate drug resistance to metronidazole. Hence, there is a clear need for the development of new antiparasitic drugs and drug targets. Methionine and adenine salvage pathways involving the products of S-adenosylmethionine (SAM, AdoMet) metabolism are a potential drug target due to the underlying autotrophy for these compounds and the importance of these metabolic pathways to the cell’s viability. Specifically, our target is the enzyme 5’-methylthioadenosine nucleosidase (MTN) which catabolizes potent product inhibitors of polyamine synthesis. The lack of structural active site homology between the analogous human enzyme 5’-methylthioadenosine phosphorylase (MTAP) and MTN makes it a promising drug target. UV spectrophotometric inhibition assays were performed with several drugs that were determined to have theoretically high binding affinities with MTN through computational prediction. Using immunofluorescence confocal images were obtained of labeled Giardia intestinalis MTN-1 and MTN-2 in order to gain insight into where MTN isozymes are located within the cell, also to develop a method to view the nucleosidases in histological slides. Several compounds showed inhibitory activity and are now under study to determine their inhibition constants and IC50 values.
Zoe Anderson, Colson Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “Investigation of Noncovalent Interactions between Diarylurea Derivatives and Anions using UV-Vis Spectroscopy”
Traditional metal carbonyl clusters (MCCs) possess the remarkable ability to undergo multiple, reversible oxidation and reduction events, which enables them to have many potential applications in electronic device manufacturing and energy storage. However, traditional synthetic methods for MCCs are inefficient and poorly selective. In our lab, a new approach to cluster synthesis has been proposed using noncovalent interactions to drive the assembly of simple metal carbonyl subunits. The purpose of my project is to determine whether UV-Vis spectroscopy can be used to investigate binding between simple anions and an isocyanide-derivatized N,N′-diarylurea compound and its coordination complexes with Group VI metal carbonyls. While this method of investigation had limitations, it lays the groundwork for future research to develop nontraditional MCCs that are more easily synthesized while electron reservoir properties are maintained.
Friday, April 26, 2019
Anthony Upshaw, Oxford Lab, Boise State Dept. of Biological Sciences
Title: “In vitro collagen gel model for tissue damage: Towards a study of Dystrophin-Glycoprotein Complex and Reactive Oxygen Species”
Duchenne’s Muscular Dystrophy is caused by a deficiency in the dystrophin protein, a component of the Dystrophin-Glycoprotein Complex (DGC), which serves as a structural link between the sarcolemma and the cytoskeleton. Neuronal Nitric Oxide Synthase is a critical enzyme in the sarcolemma responsible for catalyzing the formation of nitric oxide (NO). This enzyme is an important molecular component of the DGC. We studied the C2C12 pre-myogenic cell line by growing them in 3D collagen gels to form a model for muscle development. This muscle model maintains the cells in tension while they differentiate, and can be compared to cells grown in a stress-free environment as a control. We used the method q-RT-PCR to measure the expression of specific muscle markers in two distinct cellular environments. Histological images allowed us to assess cell morphology within each sample. This study provides preliminary data for future plans to test the effects of NO generated by plasma to answer mechanistic questions such as: 1) do increased levels of NO affect muscle-specific gene expression in the presence and absence of dystrophin, 2) will the increased NO level stabilize the DGC within the cell, and 3) are other types of muscle cells (skeletal, cardiac, and smooth) affected by increased NO in cells.
Friday, April 19, 2019
Nick Lopez, Ausman Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “Interactions between nC60 and a Model Cellular Lipid”
Abstract not available at this time.
Elena Paz Munoz, Cornell Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “MTN Knockout Attenuates Vitamin Synthesis and Global Metabolism in E. coli O157:H7”
The microbial enzyme 5’-methylthioadenosine/S-adenosylhomocysteine (MTA/SAH) nucleosidase (MTN) has three substrates MTA, SAH and 5’-deoxyadenosine (5’dADO). In each case, MTN cleaves the glycosidic linkage between the adenine ring and ribose sugar. MTN plays an essential part of methionine and purine salvage pathways, the activated methyl cycle, autoinducer-2 production, and radical S-adenosylmethionine (SAM) dependent reactions that are integral to vitamin synthesis. In this study, the impact of MTN activity on vitamin production and vitamin dependent metabolism were studied in E. coli strain O157:H7 wild type (WT) and MTN knock-out (KO) cells. Vitamins serve as cofactors for multiple pathways involved in bacterial metabolism. Proteomic studies comparing WT and KO strains have shown that the MTN KO strain expresses altered levels of enzymes involved in vitamin synthesis (thiamine, lipoate, biotin, etc.) and downstream enzymes that depend on these vitamins for activity. The results of our studies show that the activity of the biotin-containing enzyme acetyl-coA carboxylase (ACC) is reduced in the MTN KO strain. ACC is required for fatty acid biosynthesis. By biotin ELISA and ACC activity assay, we see a dramatic decrease in native biotinylation of ACC. We propose that loss of MTN activity leads to an accumulation of 5’dADO that in turn leads to product inhibition of radical SAM reactions, thus altering global metabolism through decreases in activity of vitamin dependent enzyme steps. Since MTN is only present in microbes, not humans, and central to metabolism, it may be a good target for antibiotic development. Our studies are useful in demonstrating potential mechanisms of action for such antibiotics.
Friday, April 12, 2019
Makenna Szolomayer, Cornell Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “Effect of MTN Inhibition on Vitamin Synthesis and Bacterial
Metabolism in E. coli O157:H7”
The microbial enzyme 5’-methylthioadenosine/S-adenosylhomocysteine (MTA/SAH) nucleosidase (MTN) plays an essential part in methionine and purine salvage pathways, the activated methyl cycle, autoinducer-2 production, and radical S-adenosylmethionine (SAM) dependent reactions that are integral to vitamin synthesis. In each case, MTN cleaves the glycosidic linkage between the adenine ring and ribose sugar. The microbial enzyme MTN has three substrates MTA, SAH and 5’-deoxyadenosine (5’dADO). The impact of MTN activity on vitamin production and vitamin dependent metabolism was studied in E. coli strain O157:H7 wild type (WT) and MTN knock-out (KO) cells. These vitamins serve as cofactors for multiple pathways involved in bacterial metabolism. Proteomic studies comparing WT and KO strains have shown that the MTN KO strain expresses altered levels of enzymatic activity involved in vitamin synthesis (thiamine, lipoate, biotin, etc.) and downstream vitamin dependent enzymes. Similarly, the activity of thiamine and lipoate dependent enzymes were found to be reduced. We propose that loss of MTN activity leads to an accumulation of 5’dADO that in turn leads to product inhibition of radical SAM reactions, thus altering global metabolism through decreases in activity of vitamin dependent enzyme steps. Since MTN is only present in microbes, not humans, and central to metabolism, it may be a good target for antibiotic development. Our studies are useful in demonstrating potential mechanisms of action for such antibiotics.
Bradley Lopes, King Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “Atom-Centered Solid-State DFT Calculations of Structure and
Dynamics of Molecular Crystals”
Computational chemistry is widely used within multiple disciplines of chemistry and provides theoretical data that can assist in validating the evidence obtained from experimental data. A powerful computational method is that of solid-state density functional theory due to its proven accuracy and reproducibility in calculating crystalline structures and properties. These are important parameters to consider when performing solid-state DFT calculations, primarily in determining the proper basis set and density functional that is best suited for treatment of the system of interest. In this study, four molecular crystal systems, benzoic acid, naphthalene, glucose and p-nitrophenol, were investigated using atom-centered basis sets and plane-wave basis sets using different functionals. The systems analyzed contain various intermolecular forces which will lead to results differentiated by each basis set and functional used. The atom-centered basis sets tested were 6-311G** and pob-TZVP, using functionals of varying theoretical complexity B3LYP, M06-L and PBE. The structure of each crystal system was optimized and the vibrational frequencies were calculated using the different combinations of basis sets and functionals.
Friday, April 5, 2019
After seminar April 5th- don’t forget the “Final Push BBQ” in the picnic area behind the education building. If the weather is bad, we will still cook outside, but eat in Educ 106.
Alexander Hancock, Ausman Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “Synthesis and Characterization of a Buckminsterfullerene Dimer,
Aqueous fullerene colloids have been shown to be stabilized in suspension by surface C60O molecules that result from reaction with trace atmospheric ozone. These colloids tend to crash out of suspension upon heating to ca. 50°C. To explore whether this henomenon is a result of the reaction of C60O with C60 to form C120O, C60 and C60O were mixed, dried, and baked in an attempt to create a control sample of C120O. The resulting products were separated out on a high-performance liquid chromatograph and the suspected C120O fraction was analyzed by infra-red spectroscopy and electro-spray ionization mass spectrometry.
Nathan Robinson, Lee Lab, Boise State Dept. of Chemistry & Biochemistry
Title: “Improving the Efficiency of Gold Nanoparticle Release for a
More Sensitive Catalytic DNA Sensor”
Gold nanoparticles have proven to be promising materials for colorimetric detection of DNA because of their unique optical properties. The use of gold nanoparticles in conjunction with DNA reaction networks result in the creation
of sensitive biological sensors. We are exploring disassembly-type biosensor in which NPs are released from polymer microbead template to maximize the sensitivity. We have shown sensitive detection levels are possible and are working towards a more efficient biosensor application.
Friday, March 15, 2019
Geraldin Crispin, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Title: “The Purification and Optimization of Human Carbonyl Reductase Mutants and Steady State Kinetic IC 50 Inhibition Studies”
Human carbonyl reductase (HCBR1) is an enzyme known to metabolize anthracycline chemotherapy drugs into cardiotoxic metabolites. Daunorubicin and doxorubicin are commonly used and are effective in treating cancer but dose-dependent cardiotoxicity limits its use. In the HCBR1 active site, methionine 234 (M234) is responsible for anthracycline specificity. Previous work hypothesized the M234 amino acid as sterically hindering the active site, therefore, if mutated to alanine, cysteine, or serine the smaller chains would provide greater catalytic efficiency. Site directed mutagenesis allowed M234 to be mutated and, with it, a N-terminus His-tag was attached to facilitate column purification in future work. Steady state kinetics were performed on the mutants to determine their effects on the enzyme properties and activity. Inhibitors of HCBR1 can be therapeutically useful in preventing the cardiotoxicity associated with anthracycline therapy. Several inhibitor candidate compounds were identified based on their similarity to other known inhibitors and substrates of HCBR1 that pass Lipinski’s Rule of Five, and were screened for their ability to inhibit.
Jo Williams, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Title: “The evolving role of Methionine 234 in substrate and coenzyme specificity and orientation in human carbonyl reductase I”
The NADPH-dependent reduction of anthracyclines, such as doxorubicin (DOX) and daunorubicin (DAUN), by human carbonyl reductase I (HCBR1) leads to the irreversible creation of cardiotoxic alcohol metabolites. Anthracycline-induced cardiotoxicity serves as a significant limitation to the use of anthracyclines as chemotherapeutic drugs. Based on molecular modelling studies, methionine 234 (Met234) has been postulated to play a potential role in directing substrate specificity and orientation, favoring DAUN over DOX. To investigate the role of Met234 in substrate specificity, Met234 was mutated with alanine (Met234A). Steady-state kinetic assays on DOX and DAUN, in addition to other standard substrates, with the wild-type and mutant enzymes shows that the Met234Ala mutant enzyme has decreased catalytic activity and catalytic efficiency for all substrates tested. Surprisingly, the NADPH utilization was also impaired and fluorescence quenching studies with NADPH and NADP+ show decreased Kd values for both. Molecular modeling of HCBR1 suggests a role for Met234 in mediating productive binding by NADPH.
Friday, March 29, 2019
Tyson Hardy, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Merlin Bope, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Friday, April 5, 2019
Alexander Hancock, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Nathan Robinson, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Friday, April 12, 2019
Makenna Szolomayer, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Brad Lopes, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Friday, April 19, 2019
Nick Lopez, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Elena Paz Munoz, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Friday, April 26, 2019
Anthony Upshaw, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Scott Swenson, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Friday, May 3, 2019
Tyler Gilbert, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Zoe Anderson, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Friday, February 1, 2019
Vannessa Campfield, M.S. Student, McDougal Lab, Department of Chemistry & Biochemistry, Boise State University
Title: “Microbial Diversity Observed in Swiss Cheese”
In 2017, the United States produced over 215 billion pounds of milk with 14.6 billion pounds being produced in Idaho. This dairy production led to Idaho being ranked third in the country for dairy production. Idaho manufactures over 958,000 pounds of cheese each year, which includes more than 172,000 pounds of Swiss cheese. Swiss cheese is made by separating the milk into its components, ripening the curds with added bacteria and further ripening while in storage for up to 12 months. The bacteria used during ripening metabolize compounds in the cheese matrix leading to changes such as increased carbon dioxide, specific bacterial regulation, and many others, all of which contribute to the final quality of cheese produced. This quality is graded by the USDA based on flavor, aesthetics, and structural components. We will investigate and compare the bacterial populations in Swiss cheese across manufacturers and between batches from a single manufacturer by using PCR amplification, next-generation sequencing, and bioinformatics. The resulting data will contribute to a better understanding of the bacterial-quality relationship, which will help increase the reliable production of high-quality Swiss cheese.
Friday, February 8, 2019
Riley Olsen, M.S. Student, Warner Lab, Department of Chemistry & Biochemistry, Boise State University
Title: “Rational Design of Small Molecule Inhibitors for Oncostatin M”
In 2018, it is estimated that breast cancer accounted for 30% of all diagnosed cases of cancer in woman. While the 5-year survival rate for woman without metastasis is 99%, it plummets to a mere 27% when metastasis occurs. The protein Oncostatin M (OSM) has been shown to activate several signaling pathways which promote the metastasis of breast and other cancer cells. We propose to design and synthesize small molecule inhibitors (SMIs) to fit perfectly into the predicted binding site of OSM, thus inhibiting signaling and metastasis.
Tucker Melles, M.S. Student, Callahan Lab, Department of Chemistry & Biochemistry, Boise State University
Title: “Synthesis of Peptide Nucleic Acid with Relevance to Prebiotic Chemistry”
Peptide nucleic acid (PNA) has been proposed as a possible ancestor to DNA and RNA on early Earth. PNA uses the same nucleobases as DNA/RNA, but the backbone in PNA is composed of repeating units of N-2-aminoethylglycine (AEG). The primary goal of my research will be to investigate reaction conditions that could lead to the synthesis of complete PNA monomers and oligomers, which has not been accomplished yet using conditions thought to be present on early Earth. In my seminar, I will discuss two different synthesis approaches, analytical techniques for product and structural characterization, and the significance of my planned studies.
Friday, February 15, 2019
Dr. Lisa Warner, Department of Chemistry & Biochemistry, Boise State University
Title: “Using 13C NMR to follow metabolite conversion in anaerobic bacteria”
Dr. Adam Colson, Department of Chemistry & Biochemistry, Boise State University
Title: “From Concept to Commercialization: A Case Study in Product Research and Development”
Friday, February 22, 2019
Matt Watterson and Cassidy Van Warmerdam, Payette Brewing Company, Boise, ID
Title: “Job Opportunities in the Craft Brewing Industry: A Niche Market for Chemists”
This presentation will cover opportunities in the craft beer industry; the specific avenues that brought Matt Watterson (production manager) and Cassidy Van Warmerdam (head of the QA/QC department) into their roles at Payette Brewing Company and what other opportunities students can pursue in the industry. The presentation will also cover a brief overview of the process and procedural approach to brewing at Payette Brewing and the affiliated quality controls that are built in to their work-flow.
Friday, March 1, 2019
Kim Farrar, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Title: “Trace analysis of Wine from 6000 B.C”
The Neolithic time period (10,000-3,500 BC) was the age of achievement and expansion. This period represents a transition where food-collecting cultures shifted to food-producing ones, which allowed people to establish year round settlements. Many plants were domesticated including the Eurasian grape, which is believed to be the first grape used to ferment wine. There is an ongoing archeological dig in the Republic of Georgia to investigate the earliest winemaking and the emergence of wine culture as part of G.R.A.P.E. (Gadachrili Gora Regional Archaeological Project Excavations). Pieces of pottery jars excavated from the dig site, along with corresponding soil samples, were analyzed for the presence of four characteristic grape/wine acids (tartaric acid, citric acid, malic acid, and succinic acid) by high performance liquid chromatography-mass spectrometry. All four acids were detected in trace amounts in every sample; however, there was no significant difference in the amount of acids found in the sherd samples versus the soil samples. As a result, we could not verify the presence of wine in these particular archaeological sherds.
Yume Mai, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Title: “In Vitro Analysis of Doxorubicin Analogs against Breast Cancer”
The anthracycline doxorubicin (DOX) is one of the most potent and routinely used chemotherapeutic agents in the treatment of a wide variety of human cancers. While DOX has important and substantive medical advantages, its use is complicated and restricted by the development of life-threatening heart failure. The anthracycline-induced cardiotoxic side effects lie inherently in the structure of doxorubicin. Several structural modifications were made to DOX, giving rise to a series of DOX analogs. We hypothesized that these analogs will be more effective at treating breast cancer with less cardiotoxicity. In vitro analysis of these analogs was conducted on the breast cancer cell line MDA-MB-231. The concentration of drugs required to inhibit 50% of the in vitro cell growth (IC50 value) of the aforementioned DOX analogs were studied to assess their activity and efficacy. The results of this in vitro analysis of DOX analogs lay the groundwork for the development of reduced cardiotoxicity and efficacious anticancer drugs to safely treat breast cancer and other cancers.
Friday, March 8, 2019
Spencer Gellner, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Title: “Understanding polymer wrapping kinetics for single-walled carbon nanotubes”
The goal of this research was to create a more complete understanding of the wrapping mechanism that occurs when polyvinylpyrrolidone (PVP) interacts with single-walled carbon nanotubes (SWNT). To qualitatively and quantitatively assess this, near-infrared (NIR) fluorescence was used. Looking specifically at the fluorescent semi-conducting carbon nanotubes between the 800-1400 nm. This was done while variating the weight and the ratio of PVP to SWNT. From the data collected a sum of two exponentials was initially fit to the kinetic profile. Indicating a two-step mechanism for the wrapping of SWNT with PVP. However, further research must be done to verify this claim, as the first-step of this mechanism appears to occur within the first minute of introduction of PVP into dispersed SWNT which is not easily visualized.
Alexandria Balzen, B.S. Student, Department of Chemistry & Biochemistry, Boise State University
Title: “Exploring Electron-Sink Behaviors in Molecular Iron Phosphide Clusters”
Large organometallic clusters containing transition metals and main group elements are known to exhibit multivalency, or the ability to undergo multiple electrochemical reduction events without fragmenting. However, the synthesis of such high nuclearity clusters is complicated by broad and often unpredictable product distributions. As an alternative strategy, we are investigating the synthesis and characterization of multivalent species produced through the assembly of smaller iron phosphide clusters. This presentation will describe our efforts to prepare discrete arrays of molecular iron phosphide clusters and characterize them using various analytical methods including Infrared Spectroscopy, X-ray Diffraction and Cyclic Voltammetry.