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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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report
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Author
Title
Subject
Date
Publication Type
426
Page 28
427
Page 119
428
Fay, Marta Marie
Context-dependent modulation of the tumor suppressor programed cell death 4 (PDCD4) by argenine methylation
2013-12
dissertation
429
Page 111
430
Page 232
431
Page 32
432
Page 34
433
Page 4
434
Page 42
435
Page 43
436
Hoffmann, Randi
The impact of exercise on hematopoietic stem cell patients
Exercise; Fatigue; Function; Stem cell transplant; Theory of planned behavior
2013-08
dissertation
437
Bloom, Rosaleen Duggan
Patients' and caregivers' experience of social support on caringbridge
Nursing; Web Studies; Oncology
2017
dissertation
438
Page 8
439
Biltaji, Eman
Clinical utility of multigene versus single gene genomic profiling in metastatic colorectal cancer
Clinical Utility; Colorectal cancer; Comparative Effectiveness Research; Genetic testing; Pharmacogenetics; Precision medicine
2016
dissertation
440
Page 151
441
Page 54
442
Page 93
443
Page 132
444
Page 15
445
Page 19
446
Page 75
447
Page 77
448
Page 147
449
Subrahmanyam, Nithya Bala
Water soluble polymer-collagen hybridizing peptide conjugates for targeting the tumor extracellular matrix
2023
dissertation
450
Page 160
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