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Chapter 1 focuses on the inhibition of the β-catenin/B-Cell lymphoma 9 proteinprotein interaction. This protein-protein interaction is found in Wnt signaling and has been strongly linked to cancer. To inhibit the interaction, molecules were computationally designed, synthesized and tested. A series of 33 final compounds was synthesized, resulting in a lead molecule with an inhibition constant of 5.2 μM. The binding mode of this molecule was validated through the structure activity relationship of the series as well as mutational studies. The lead molecule was shown to exhibit 98-fold selectivity for the β-catenin/B-Cell lymphoma 9 interaction over the β-catenin/E-cadherin interaction, inhibit the Wnt pathway in a cell based assay and inhibit the growth of Wnt/β-catenin-dependent cancer cells. Chapter 2 describes an attempt to overexpress and purify the ethylene receptor, a membrane protein found in plants critical to all stages of plant life. There are major unanswered questions involving the ethylene receptor, but most important is the nature of the binding interaction between ethylene and the receptor. We intended to characterize the interaction using a variety of spectral techniques, which would require large amounts of protein. Several strategies to express and purify the receptor were pursued. Chapter 3 lays the foundation for using Stark vibrational spectroscopy to more thoroughly understand the mechanism of proton pumping. Stark vibrational probes were installed in the proton pump ubiquinol oxidase. Functional protein containing the probes iv was successfully expressed and purified. The probes were then utilized to survey the electric field within the proton pump. Changes in electric field were detected in multiple locations and synchronistic results were observed for probes positioned in the same region of the protein. The presented work was highly decoupled and covered a broad area. Completion required efforts in organic synthesis, molecular biology, protein chemistry and spectroscopy. Overall, important foundational achievements were made on several challenging and significant systems.
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honors thesis
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report
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1
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1
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1
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1
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1
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Author
Title
Subject
Date
Publication Type
151
Page 103
152
Page 184
153
Page 205
154
Page 89
155
Page 175
156
Emery, Gwyn M.
Screening behaviors among African American women at high risk for breast cancer: do beliefs about God matter?
Black people; Medicine, Religious Philosophies
2000-08
thesis
157
Page 66
158
Mulrooney, Tamsin.
The lived experience of cognitive impairment in women treated with chemotherapy for breast cancer.
Psychological Aspects; Breast Cancer
2007-12
dissertation
159
Page 149
160
Page 35
161
Page 67
162
Page 110
163
Page 4
164
Greaves, William Walter
Relationship between lung cancer and distance of residence from a nonferrous smelter.
Etiology; Lungs; Cancer
1980-08
thesis
165
Gudgeon, James Michael
Optimizing lynch syndrome index case finding in endometrial cancer
2018
dissertation
166
Page 146
167
Page 65
168
McQuerry, Jasmine Ariel
Leveraging phenotypic profiling using omics analyses to combat refractory breast cancers
2020
dissertation
169
Page 120
170
Page 130
171
Page 156
172
Page 16
173
Page 168
174
Page 199
175
Page 34
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