Browsing Medicinal chemistry by Title
Now showing items 28-47 of 54
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In vitro and in vivo studies of methadone metabolism and pharmacokinetics
Methadone ((R,S)-6-dimethylamino-4, 4-diphenyl-3-heptanone) is a synthetic mu-opioid receptor agonist developed in Germany during World War II as a replacement for morphine. Methadone is currently used to aid in opioid ... -
Interactions of Cytochrome P450 3A4 with Phospholipid Bilayer Nanodiscs
Cytochrome P450s (CYPs) are the major drug-metabolizing enzyme in humans. Cytochrome P450 3A4 (CYP3A4), in particular, is responsible for approximately half of all CYP-mediated drug metabolism. In mammals, drug-metabolizing ... -
Interactions of the Amyloid-forming Peptide PAP248-286 with Lipid Membranes: Relating Biophysical Mechanism to Biological Activities
The interactions of membrane active peptides with lipid membranes are critical to both normal biological function and to the pathogenesis of many debilitating diseases. Antimicrobial peptides (AMPs), important players in ... -
Investigating mechanisms of neutralization of staph enterotoxin B
Staphylococcal enterotoxin B (SEB) is a small, secreted protein that causes food poisoning-like symptoms and can be lethal in microgram amounts. SEB elicits a profound immune response via the bridging of major histocompatibility ... -
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 ... -
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 ... -
Ligand and Protein Dynamics of CYP3A4
Cytochrome P450 3A4 (CYP3A4) dominates drug metabolism in humans. Examples of promiscuity (binding and catalytic) and allosterism in CYP3A4 are ubiquitous but poorly understood. This work is dedicated to improving our ... -
Lipid Peroxidation Mechanisms and Their Contribution to Ferroptosis
The attack of reactive oxygen species (ROS) on reactive lipids leads to free radical chain reactions with molecular oxygen, a process termed lipid peroxidation. Increased lipid peroxidation is associated with many human ... -
Mechanisms of antibody-mediated neutralization targeting viral glycoproteins
The antibody response against viral glycoproteins is important for preventing many viral infections but we lack a comprehensive understanding of the mechanisms by which antibodies act. Furthermore, the immense antigenic ... -
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 ... -
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, ... -
METTL7 Alkyl Thiol Methyltransferases: Implications in Drug Metabolism and Human Health
Thiol metabolism in humans is catalyzed by two enzymes, thiopurine methyltransferase (TPMT) and thiol methyltransferase (TMT). TPMT selectively methylates thiopurine compound while TMT is selective for aliphatic thiol ... -
Non-Dissociative Sequential Metabolism of Enoxacin to a Metabolic Intermediate Complex with Cytochrome P450 1A2
Cytochrome P450 enzymes constitute a superfamily of isoforms which accelerate the removal of foreign compounds from the body through oxidative biotransformation to generate polar metabolites that are more readily excreted ... -
Pushing the limits of Structural Mass Spectrometry to Characterize the Viral Packaging Motor
Assessing protein structure is a difficult undertaking, yet is often required for a complete mechanistic understand of how a protein functions. The traditional techniques used to assess protein structure are X-ray ... -
Role of Epoxyeicosatrienoic Acids in Protecting Against Ischemic Cardiomyopathy
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid (AA) epoxidation with important cardioprotective and signaling properties. AA is a twenty carbon ω-6 polyunsaturated fatty acid containing four cis-double ... -
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) ... -
Selectivity and Mechanisms of Human Cytochrome P450 Inhibition by Chlormethiazole
The cytochrome P450 (CYP) superfamily of enzymes are heme containing enzymes that primarily perform oxidative reactions to a variety of substrates, including small molecule drugs and other xenobiotics. Formation of polar ... -
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 ... -
Structural Dynamics and Reaction Reversibility of Specific vs. Promiscuous Detoxification Enzymes
Detoxification enzymes occupy a unique niche in biology. Unlike most enzymes with defined roles in biochemical pathways, detoxification enzymes have evolved to bind and metabolize many chemically unrelated structures ¬– ...