Weekly: ILC 118 – 1:30 pm to 2:20 pm
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.