Browsing Medicinal chemistry by Title
Now showing items 17-36 of 54
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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 ... -
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 ... -
Determination of Xenobiotic and Endogenous Metabolites Using Ion Mobility-Mass Spectrometry and Machine Learning
Confident identification of xenobiotic and endogenous metabolites is central to applications including metabolomics, lipidomics, and drug metabolism studies. The integration of ion mobility spectroscopy with mass spectrometry ... -
Drug combination nanoparticles targeted to ICAM-1 on breast cancer cells enhance cellular drug exposure in vitro and in mouse model
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of 3 cell receptors--the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor-2 (Her2) --that ... -
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 ... -
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 ... -
Genetic and Environmental Factors Affecting Hemostasis in Yup'ik People
Fish oil has been widely studied for its protective effects against heart disease. These effects are attributed to omega-3 PUFA content, which are also found in sea mammals in addition to fish. The mechanism by which ... -
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 ...