2012 Summer Research Projects
Synthesis of N-Alkyl Pyridone Containing β- and γ-Amino Acids
Professor Carolyn Anderson, John LaGrand and David Wierenga
Organic synthesis is a powerful technique that allows access to a wide range of different structural motifs. In this project, we are working to develop a method for the synthesis of N-alkyl pyridone containing β- and γ-amino acids – homologues of the natural amino acids, which contain an interesting functional group, found in a series of pharmacologically active compounds. To date, we have discovered an important intermediate in route to these species and have begun to optimize its synthesis. The students working in this area will continue to seek conditions for the preparation of this intermediate and its conversion into the desired amino acids. The students will gain experience with synthetic organic chemistry techniques, including: running reactions, purification, organic spectroscopy, and experimental design.
Gold-catalyzed Rearrangement of N-Propargyloxypyridines
Professor Carolyn Anderson and Emily Rhude
Organic synthesis is a powerful technique that allows access to a wide range of different structural motifs. In this project, we are working to advance a method for the synthesis of N-substituted pyridones; an interesting functional group found in a series of pharmacologically interesting compounds. To date, we have developed a new gold(III)-catalyzed method for accessing this motif by rearranging a related system. The student working in this area will be responsible for exploring and optimizing a related gold(I)-catalyzed rearrangement. The student will gain experience with synthetic organic chemistry techniques, including: running reactions, purification, organic spectroscopy, and experimental design.
Synthesis of N-Alkyl Pyridones via Gold(I)-Catalysis
Prof. Carolyn Anderson and Nick Vryhof
Organic synthesis is a powerful technique that allows access to a wide range of different structural motifs. In this project, we are working to develop a method for the synthesis of N-alkyl pyridone containing α- and β-amino acids – homologues of the natural amino acids, which contain an interesting functional group, found in a series of pharmacologically active compounds. To date, we have discovered an important intermediate in route to these species and have begun to optimize its synthesis. The students working in this area will continue to seek conditions for the preparation of this intermediate and its conversion into the desired amino acids. The students will gain experience with synthetic organic chemistry techniques, including: running reactions, purification, organic spectroscopy, and experimental design.
Characterization of Splice Variants from Zebrafish
Prof. Eric Arnoys and Elizabeth DeGroot
We will characterize the folding and protein-protein interactions of three splicing variants of a potential splicing factor from zebrafish. The student will examine protein expression in adult tissue, observe expression of fluorescently tagged proteins in cell culture, and purify recombinant proteins for binding studies.
Watching Membrane Proteins in Real Time
Prof. Eric Arnoys, Prof. Larry Louters and Riemer Praamsma
We will characterize the behavior of several membrane-bound proteins in living cells with state-of-the-art techniques to examine their cellular localization, mobility, and interactions with other proteins. Protein targets have been tagged with fluorescent proteins so that they can be viewed in living systems. We will also examine what effect extracellular signals have on the proteins' behavior.
Proteins as Antioxidants Using Tyrosine and Cysteine Sidechains
Prof. David Benson, Anand Divakaran, Taylor Hegg, Ryan Martinie, Nathanael Myton, and Elizabeth Porter
This project will look at three proteins (cysteine dioxygenase, hemoglobin, and a protein named BF4112). Each of these proteins form or are thought to form a covalent bond between specific tyrosine (phenol) and cysteine (sulfhydryl) sidechains in these proteins. We term this covalent bonded pair of sidechains a Tyr-Cys crosslink. Tyr-Cys crosslinks are known in four naturally occurring proteins and are members of a growing class of post-translational modifications. Tyr-Cys crosslinks are chemically intriguing because when placed next to a mononuclear iron or copper center, two-electron oxidations are readily catalyzed. Last summer the Benson lab documented the fifth protein with a Tyr-Cys crosslink, BF4112. Hemoglobin and cysteine dioxygenase will be examined this summer as well as BF4112. Cysteine dioxygenase is known to have a Tyr-Cys crosslink but the function is unknown. We believe Tyr-Cys in cysteine dioxygenase may regulate the lifespan of the protein; which is crucial in minimizing neurological disorders. Finally hemoglobin is well studied within the red blood cell, however we have found conditions that form a Tyr-Cys in hemoglobin that are consistent with after red cell lysis. Again we believe there is an anti-oxidant role for Tyr-Cys, after formed, in hemoglobin as well. These sub-projects tie together to test our hypothesis that crosslinked amino acid sidechains, such as Tyr-Cys, could form an additional layer of cellular protection from oxidative stress.
Cooperativity in Hydrogen Bonding
Prof. Roger DeKock and John Strikwerda
For several years we have performed theoretical studies that relate to cooperativity in hydrogen bonding. For example, we examine molecular cubes with the formula NH3(H2O)7. We believe that these small cubes can serve as prototypes for cooperativity in hydrogen bonded networks in real chemical systems, such as ammonia, NH3, in water. We have completed similar studies on the thirty nine cubes of HF(H2O)7. Additional studies on these systems need to be completed. Those additional studies would be the focus of the summer 2012 work.
Catalytic C–H Bond Activation
Prof. Roger DeKock and Jonathon Vandezande
For several years we have performed theoretical studies that investigate the activation of C–H bonds by transition metal complexes. The present study extends this ongoing work. We intend to focus on computer modeling of the binding of simple olefins (e.g. ethene) with di-iridium complexes. The research group of Martin Cowie at the University of Alberta has unpublished experimental observations on such activation. Our work will be to map out the potential energy surface for this reaction.
Understanding the Motives and Barriers to Two-Way Faculty/Student Feedback in Science, Math, and Engineering
Prof. Herb Fynewever and Simon Veldkamp
Usually when students are learning science, math, and engineering they reveal their thinking to the instructor and the instructor uses this information to give feedback to the students. Often, however, this two-way communication is limited to formal assessments such as quizzes and exams, which happen after most of the learning has happened. Research has shown that there are many effective ways to better integrate this communication into the learning process (e.g. interactive classroom delivery and activity) realizing significant gains in student learning. Further research is needed to determine what the barriers are to two-way communication and to devise strategies to remedy these barriers. In this research, students will analyze data from classroom observations and interviews with faculty and students to detect and classify these barriers.
Activation of Glucose Transport Activity of GLUT1: Does it Form a Tetramer?
Prof. Larry Louters, Ola Alabi and Ben Kuiper
The transport activity of GLUT1 appears to be activated when an internal disulfide bond forms in GLUT1 which triggers it to aggregate with other GLUT1 proteins. We have evidence that formation of a disulfide activates transport, but we have no direct evidence that it forms a complex. We will use fixation chemistry (eg formaldehyde) to stabilize the active form and isolate the complex by immunoprecipitation. We will determine if there is a difference in the size of GLUT1 in the active and inactive states.
Effects of Curcumin (from the spice, Tumeric) on Glucose Uptake
Prof. Larry Louters and Stephen Gunnink
Curcumin, an ingredient in the Indian spice, tumeric, has a molcular structure that is reactive with thiols. GLUT1, the major glucose transporter, is thought to be activated by the formation of a disulfide bond. We hypothesize that curcumin will alter the glucose transport activity of GLUT1 in L929 fibroblast cells.
Photochemistry: Research in Fluorescence in Sycamore Wood and Photoelimination in Acetylacetone.
Prof. Mark Muyskens, Andrea Bootsma and Brett DeVries
There are two areas of photochemistry that will be investigated. One area is to investigate the chemical structure of the highly fluorescent components of the aqueous extract of sycamore wood. These compounds have not yet been investigated. The work involves liquid chromatography for separation and fluorescence spectroscopy. The other area will use computational tools to model the kinetic and molecular structural details of a gas-phase photochemical reaction. My research has experimental results from the ultraviolet laser photoelimination of hydrogen fluoride from fluorine containing acetylacetone in the gas phase. The work will be greatly assisted by developing models related to the data.
Characterizing the Binding Interaction of Insulin with G-Quadruplex DNA: From Single Molecule to Bulk Measurements
Prof. Kumar Sinniah and Nicole Michmerhuizen
G-quadruplexes are noncanonical DNA structures formed from guanine-rich DNA sequences in the presence of monovalent cations such as potassium or sodium ions. These structures are of significant interest due to their possible role in biological processes. Since the human genome contains hundreds of thousands of sequences that have the potential to form quadruplexes, proteins that bind to G-quadruplex DNA may provide a clue to the role of G-quadruplex DNA in biology. This summer we will probe the biophysical interactions between the protein insulin and G-quadruplex DNA. This project is suitable for a student interested in biochemistry, chemistry, or biology.
Characterizing Riboflavin Conjugated Nanoparticles for Targeted Drug Delivery in Cancer Therapy
Prof. Kumar Sinniah, Abigail Leistra and Amanda Witte
Riboflavin (RF) receptors have been found to overexpress in prostate and breast cancer cells. RF receptors can be targeted for selective delivery of anticancer drug molecules. The past summer we characterized two RF conjugated dendrimer series for targeting the RF receptor. We determined that one series of dendrimer conjugates based on the orientation of RF attachment to the dendrimer performed better at binding to the RF receptor. This summer we hope to extend this work to study both the monovalent and multivalent interactions between RF and its receptor using single molecule and bulk ensemble methods. This project is suitable for a student interested in biomedicine/biochemistry/biology.
Aromatic Interactions as Elements of Structure, Stability and Function
Prof. Chad Tatko, Andrew Roth, Jin Sung and Caleb Uitvlugt
Aromatic interactions are ubiquitous in chemistry and biology. Through the synthesis of model peptides their role in beta-hairpin structure and stability will be explored. By positioning lateral pairs of aromatic residues in a beta-hairpin the impact of electronic differences will be used to alter pKa and redox potentials. Additionally, the use of peptides as scaffolds for molecular recognition of exogenous aromatic compounds.
Nanomolecular Building Projects
Doug VanderGriend, Emily Golz, Shelby Lofthus, Michael Lubben and Liz Vincent
Understanding and controlling the synthesis of supramolecules is a key goal of nanotechnology. The students working on this project will use UV-vis spectroscopy and mass spectrometry (at Mchigan State University) to investigate the solution chemistry of transition metal cations, which typically bond to 4-6 ligand molecules in various geometries. These different building blocks can be used to make nanocontainers, nanomachines, and thermochromic solutions. A significant element of the research also involves modelling multi-equilibria systems. This includes modeling artificial data to probe the limits of our mathematical techniques so that we can better evaluate our models of real data.
I anticipate that the students will not only get ample hands on experience with making up solutions and mastering several analytical instruments, but also have a chance to interact with our collaborators at graduate and industrial labs. It is ideal for students who have completed general chemistry. Special consideration will be given to students with interest in mathematics and/or computer science.
Development of Web-based Platform for Analytical Chemistry Program
Prof. Doug Vander Griend and Matthew Haveman
Understanding and controlling the synthesis of supramolecules is a key goal of nanotechnology. In our chemistry lab we use UV-vis spectroscopy to investigate the solution chemistry of transition metal cations, which typically bond to 4-6 ligand molecules in various geometries. These different building blocks can be used to make nanocontainers, nanomachines, and thermochromic solutions. The key is that we model our data using advanced mathematical techniques via a computer program called Sivvu, which is written in the Matlab environment. The student would learn the necessary chemistry, but focus on transforming our computational technology to a standalone executable and java script. This task will involve learning to use Matlab and Matlab compiler. Furthermore the student will get a change to modify the architecture of the program as necessary. Special consideration will be given to students with interest in mathematics and/or computer science and who have completed general chemistry.