Browsing Medicinal chemistry by Title
Now showing items 1-20 of 54
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Advancing Hydrogen Deuterium Exchange Mass Spectrometry Through the development of Novel Internal Exchange Reporters
University of WashingtonAbstract Advancing Hydrogen Deuterium Exchange Mass Spectrometry Through the development of Novel Internal Exchange Reporters Taylor Murphree Chair of Supervisory committee: Miklos Guttman Medicinal ... -
Autocatalytic mechanism and functional consequences of covalent heme attachment in CYP4B1
(2005)The studies presented in this dissertation establish the precise structure and sites of attachment of the covalent linkage that binds heme to CYP4B1, reveal a viable autocatalytic mechanism for its formation, and evaluate ... -
Biochemical and Mechanistic Studies of the Interactions Between Vitamin K Antagonists and Vitamin K Epoxide Reductase
(2013-02-25)The studies that are presented in this dissertation have; (i) established a mechanism by which warfarin dose response is modulated by VKORC1 genotype under optimized conditions for kinetic analysis of human vitamin K epoxide ... -
Biochemical Characterization of Drug Metabolizing Alkyl Thiol Methyltransferase 1A and 1B
In humans, S-methylation of aromatic and alkyl thiols is catalyzed by thiopurine methyltransferase (TPMT), and a putative enzyme(s) thought to be responsible for alkyl thiol methyltransferase (TMT) activity. In this work, ... -
Biophysical and Structural Approaches to Characterize the Mechanism of P-glycoprotein, a Multidrug Efflux Transporter
P-glycoprotein (P-gp), an ATP Binding Cassette transporter (ABCB1), plays an important role in multidrug resistance in cancers and clinical drug interactions. P-gp utilizes the energy from ATP hydrolysis to drive conformational ... -
Biophysical Approaches for the Development of Stable, Long-Lived, Multi-Functional, and Potent Antibody Therapeutics
Antibody-based proteins have become an important class of biologic therapeutics, due in large part to the stability, specificity, and adaptability of the antibody framework. Indeed, antibodies not only have the inherent ... -
A Biophysical Rationalization of Type II and Reverse Type I Inhibitor Interactions in CYP450 with Implications for Enzyme Function
(2013-11-14)This work is a characterization of small molecule azole-based inhibitor interactions in cytochrome P450 (CYP) using a complement of biophysical methodologies to provide molecular level details of the underappreciated ... -
Bridging HIV neutralization sensitivities and Env dynamic phenotypes across genetically diverse variants
The envelope glycoprotein (Env) is the sole target for neutralizing antibodies against HIV and the most rapidly evolving, variable part of the virus. High-resolution structures of Env trimers captured in the prefusion, ... -
Chaperone effects on tau amyloid formation
Tau is a microtubule-associated protein that forms insoluble amyloid fibrils in a set of neurodegenerative disorders termed tauopathies, which include Alzheimer’s disease, frontotemporal dementia, and chronic traumatic ... -
Characterizing the role of CYP2J2 in clear cell renal cell carcinoma and TKI-mediated cardiotoxicity
CYP2J2 is the only member of the human CYP2J family, and its expression is largely extrahepatic. The highest expression of human CYP2J2 is in the heart, where its major endogenous function as an arachidonic acid (AA) ... -
Conformational Heterogeneity and Catalytic Promiscuity in Glutathione Transferases
(2013-02-25)Enzymological paradigms have shifted recently to acknowledge the biological importance of catalytic promiscuity. Detoxification enzymes, such as glutathione transferases, are known to be highly promiscuous. One common ... -
Controlled Assembly of Viral Surface Proteins into Biological Nanoparticles
(2014-02-24)In recent years, therapeutic use of engineered particles on the 1-1,000 nm scale has gained popularity; these nanoparticles have been developed for use in drug delivery, gene therapy, vaccine preparation, and diagnostics. ... -
Cooperative Assembly of Terminase and Integration Host Factor at the Packaging Initiation Site of Bacteriophage Lambda
(2013-11-14)Packaging of viral genomes into procapsids by terminase enzymes is conserved in many DNA viruses. Terminases bind to linear concatemers of replicated viral genomes and concomitantly excise (mature) and package a single ... -
CYP2J2 Regulation in Adult Ventricular Myocytes: Cell-wide Consequences and Effects on Stress Responses
Cytochrome P450 2J2 (CYP2J2) is drug metabolizing member of the cytochrome P450 (CYP) superfamily. While CYPs involved in drug metabolism are generally highly expressed in “drug clearance” organs such as the small intestine, ... -
Cytochrome P450 family 4 enzymes in cancer: Leveraging bioactivation for therapeutic potential
Cytochrome P450 (CYP) enzymes are a critical family of hemoproteins that are involved in the metabolism of both xenobiotic and endogenous molecules. The CYP4 family constitutes thirteen enzymes in humans that are typically ... -
The Cytochrome P450 Family 4 Enzymes: Focus on Inhibition by Formamdioxime Analogues and Metabolism of Vitamin K
(2013-07-25)The studies presented in this dissertation explore Cytochrome P450 family 4 (CYP4) enzyme inhibition and metabolism. The structure-activity relationships between CYP4 enzymes and the potent formamidoxime inhibitor, HET0016, ... -
Data-independent mass spectrometry strategies for the identification of atRA-mediated protein signatures of differential cellular response
(2013-11-14)Mass spectrometry is a powerful proteomics tool. Advancements in instrumentation and data acquisition techniques allow researchers to identify and quantify thousands of proteins from cellular samples in a high throughput ... -
Decoding the Structural Determinants of Hemagglutinin Mediated Influenza Entry and Antigenicity
The fusion glycoproteins found on the surface of enveloped viruses enable the delivery of the viral genome into the host cell by facilitating the merger of the viral membrane with the host cell membrane, an essential step ... -
Defining the Relationship between the Bioactivation of Lapatinib by CYP3A and Lapatinib-Induced Hepatotoxicity
Lapatinib was the first orally active dual tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR, ErbB1) and human epidermal receptor 2 (HER2, ErbB2) to be approved by the US Food and Drug Administration ... -
Defining the Structural Features and Functional Characteristics of Complement-Active IgM
Immunoglobulin M (IgM) is an extremely important, yet surprisingly under-studied glycoprotein that is shared among all vertebrates on an evolutionary timeline spanning more than 500 million years. In addition to the ...