Browsing Medicinal chemistry by Issue Date
Now showing items 1-20 of 54
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Mechanisms of oxidation of acetaminophen
(1984)The metabolism of drugs and other xenobiotics normally expediates elimination and detoxification. However, in some instances inert compounds are transformed into potent alkylating or arylating agents capable of eliciting ... -
Defining the use of midazolam as a probe of CYP3A4 activity: sensitive quantitation of the metabolites and characterization of mechanism-based inactivation
(1996)A highly sensitive GC NCI/MS assay was developed for midazolam metabolites. The limit of quantitation was 0.3 ng/mL. This assay allowed the determination of kinetic parameters for metabolite formation from in vitro incubations ... -
Experimental and computational investigations of the stability and dynamics of cytochrome bb5s
(1998)Both computational and experimental approaches were used to study cytochrome b$\sb5.$ The goal was to investigate protein dynamics and how they may relate to stability and biological function.Computational studies used ... -
The functional role of Phe-10 and the anomalous Tyr-9 pKa in glutathione S-transferase A1-1
(2002)As the most abundant isoform of GST in the liver, the GST A1-1 is the major catalyst of detoxification. This isoform is of particular interest because it exhibits an unusually low pKa (∼8.1--8.3) of active site Tyr-9 and ... -
Enzymology at the dimer interface of cytosolic glutathione S-transferases
(2002)The glutathione S-transferases (GSTs) represent a family of cytosolic enzymes whose primary function is the detoxification of electrophilic chemical species of endogenous and exogenous origin. As described in the introductory ... -
Mechanistic investigation of cytochrome P450 1A2 catalyzed metabolism of 8-alkylxanthines
(2003)The mechanism of CYP1A2 (cytochrome P450 1A2) catalyzed metabolism of 8-alkylxanthines is explored using deuterium isotope effect studies and isotope tracing experiments with an 8-isopropyl analog (isopropylcyclohexylline, ... -
The involvement of mitochondria in the cell death process: communication from mitochondria to the nucleus
(2003)A thorough understanding of the mechanisms of cell death could open the door to numerous opportunities for therapeutic modulation. In addition to disease state treatment options, cell death modulation may also have benefit ... -
Structural immunology of humoral and cellular recognition of a MUC1 breast cancer antigen
(2003)MUC1 mucins have recently been the target of breast cancer vaccine trials. MUC1 peptide vaccine studies in mice have resulted in rejection of solid tumor and protection from further tumor challenge. These results represent ... -
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 ... -
An investigation of cellular responses to tetrafluoroethylcysteine-induced mitochondrial dysfunction
(2005)Several disease states and chemical-induced toxicities are mediated through an early mitochondrial dysfunction. A better understanding of the molecular and biochemical events that transpire during such mitochondrial damage ... -
Investigation of Surface Interactions between Cytochrome b5 and Major Cytochrome P450 Isoforms
(2012-09-13)Cytochrome b5 (cyt b5 or holo b5) is known as one of the key components in the microsomal cytochrome P450 (CYP) monooxygenase system that metabolizes structurally diverse endogenous and exogenous compounds. It has been ... -
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 ... -
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 ... -
Species Differences in the Metabolism and Toxicity of 4-Ipomeanol
(2013-04-17)The studies presented in this dissertation investigate the enzymatic basis for the species differences in target organ toxicity of the pro-toxin, 4-ipomeanol (IPO). <italic>In vitro</italic> studies that monitored the ... -
Searching for Protein Biomarkers of Disease in Bronchoalveolar Lavage Fluid
(2013-04-17)Respiratory diseases minimize gas exchange at the alveoli and complicate the mechanics of breathing. Bronchoalveolar lavage fluid (BALF) is capable of sampling the components of the alveolar epithelial lining fluid (ELF) ... -
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 ... -
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 ... -
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 ... -
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. ...