Biochemistry, Biophysics, and Structural Biology Commons^™

Biological Activity Of A Set Of New Copper(Ii) Complexes: Toward Understanding Structure-Reactivity Correlations, Chelsea Aitken

Honors Theses

Cisplatin, carboplatin and oxaliplatin are all platinum-containing complexes that have been approved for use as chemotherapy drugs. The success of these complexes as well as their downfalls have sparked interest into alternative transition metal based compounds as potential chemotherapeutic agents. The use of platinum based complexes in cancer treatment has faced complications including cytotoxicity and drug resistance. The use of copper(II) as an alternative metal center is of specific interest because of bioavailability and elevated concentrations of this metal ion within tumor cells. Three copper complexes that utilize a nitrogen based ligand system, two of which contain a thiazole moiety …

Investigation Of The Mechanism Of Binding Of Perfluoroalkyl Acids With Human Serum Albumin Using An Improved Approach To Equilibrium Dialysis, Michael Morris

Honors Theses

Perfluoroalkyl acids (PFAAs) are used to produce many consumer products, but their bioaccumulative and toxic properties and their global persistence in the environment are major concerns. In particular, PFAAs have been shown to accumulate in the blood, liver, and kidneys of organisms. As such, it is important to elucidate the toxicokinetics of PFAAs by quantitatively and qualitatively characterizing the binding mechanism of PFAAs to human serum albumin (HSA). In this study, the binding of PFAAs to HSA are studied via a high-throughput equilibrium dialysis method that utilizes the 96-well Equilibrium Dialyzer coupled with sample quantitation using liquid chromatography tandem-mass spectrometry …

Cloning, Expression And Interaction Studies Of The Potential Rubisco Activase Cbbq, Salma A. Dawoud

Honors Theses

Carboxysomes are polyhedral microcompartments found in all cyanobacteria and in many chemoautotrophs. Within their shell they contain the enzyme ribulose-1, 5-bisphosphate carboxylase/oxygenase (RubisCO), which fixes CO₂. Downstream of the carboxysome operon there is another gene cluster containing several genes that may enhance carboxysome function. Two of these genes, cbbQ and cbbO, encode potential RubisCO activases. Using recombinant CbbQ and CbbO protein, and RubisCO isolated from carboxysomes the interaction between these proteins was studied. The CbbO and CbbQ proteins were both His tagged, allowing them to be purified with Ni²⁺-NTA column chromatography. Each of these tagged …

Optimization Of A Chemical Genetic Screen To Identify Druggable Targets In U138 Cells Treated With Laromustine, Kathryn Coe

Honors Theses

Laromustine is an experimental sulfonylhydrazine prodrug used in late-stage clinical studies against acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). Despite initial promise for both indications, clinical trials for GBM have not been as successful as those for AML. To investigate methods for improving the effectiveness of laromustine in GBM and to learn more about the mechanism of action of laromustine, a chemical genetic screen will be conducted to identify agents that sensitize GBM cells to the anti-proliferative effects of laromustine. The library, which will include approximately 450 FDA-approved drugs, will be screened using a newly optimized high throughput assay …

Do The Inter-Nucleotide Domain Loops Act As An Entropic Sink In The Catalytic Activity Of 3-Phosphoglycerate Dehydrogenase (3pgdh)?, Cristina Adelia Meeham

Honors Theses

In protein science the relationship between protein dynamics and catalytic activity are the subject of considerable contemporary interest. Although protein motions are frequently observed during ligand binding and release steps, the contribution of protein motions to the catalysis of bond making/breaking processes is more difficult to probe and verify. Currently, the field of protein science is trying to uncover the deeper role that dynamics plays in the catalytic activity and allosteric regulation of proteins and to better understand how to more effectively and efficiently target proteins in cancer therapeutics and other metabolic pathways.

One-Pot Heteroconjugate Addition-Diels-Alder Reactions And Acetate-Catalyzed Aldol Reactions Of Α-Silyl Nitriles, Carly Mueller

Honors Theses

1. A one-pot three-step Diels–Alder reaction sequence of ethyl propiolate and thiols can be performed to produce high yields of complex bicyclic products. A KOt-Bu-catalyzed thioconjugate addition of thiols to enoates, oxidation of the generated thioenoate by mCPBA, and Li-catalyzed Diels–Alder addition of cyclopentadiene occur in situ, without any purification of intermediates.
2. Stereoselectivity of the Diels–Alder product was examined by utilizing a chiral sulfone substrate. It was determined that these substrates were unable to provide significant stereochemical control.
3. Silylation of 3-phenylpropionitrile is achieved at the α-position with trimethylsilyl trifluoromethanesulfonate and trialkylamine base. Catalyzed by tetrabutylammonium acetate (2.5 mol%), …

A Conservative Isoleucine To Leucine Mutation Of Klentaq1 Dna Polymerase 1 Induces Conformational Change For Cold-Sensitive Phenotype, Emma Caroline Materne

Honors Theses

Polymerase Chain Reaction (PCR) typically employs the Taq or Klentaq1 DNA polymerase from Thermus aquaticus to elongate short sequences of DNA during DNA amplification. Both Taq and Klentaq1 retain activity at room temperature. During assembly of PCR at room temperature, the activity of Taq and Klentaq1 can result in spurious products due to elongation of primers bound to non-target sequences. A mutation of isoleucine to leucine at position 707 of Klentaq1 results in slowing of the enzyme at room temperature without compromising the fidelity of the enzyme. To understand how a mutation over 20Å from the active site can affect …

Formyl Group Activation Of Bromopyrrole Suzuki Cross-Coupling: Application To A Formal Synthesis Of Lamellarin G Trimethyl Ether, Andrew Harrison

Honors Theses

Many biologically interesting compounds have been isolated from marine natural products, many of which contain characteristic pyrroles. Compounds such as polycitones, storniamides, ningalins, and lamellarins have been of particular interest for synthesis due to their vast pharmaceutical potential including the ability to fight tumors as well as induce cytolysis of drug resistant cancer cell lines. Previous studies on the synthesis of Lamellarin G trimethyl ether by the Gupton Group have relied upon vinylogous amide derivatives as building blocks.2 A new pathway utilizing a formylated pyrrole ring provides an interesting method for the synthesis of Lamellarin G trimethyl ether. Regioselective Suzuki …