First Review Of Equilibrium Landscape Of Ingress/Egress Channels And Gating Residues Of The Cytochrome P450 3a4,
2023
Southern Illinois University Edwardsville
First Review Of Equilibrium Landscape Of Ingress/Egress Channels And Gating Residues Of The Cytochrome P450 3a4, Edward Ackad Ph.D, Maria Kontoyianni
SIUE Faculty Research, Scholarship, and Creative Activity
The review document and changes made to "Equilibrium Landscape of Ingress/Egress Channels and Gating Residues of the Cytochrome P450 3A4".
Synthesis And Self-Assembling Properties Of Carbohydrate- And Diarylethene-Based Photoswitchable Molecular Gelators,
2023
Old Dominion University
Synthesis And Self-Assembling Properties Of Carbohydrate- And Diarylethene-Based Photoswitchable Molecular Gelators, Pramod Aryal, Joedian Morris, Surya B. Adhikari, Jonathan Bietsch, Guijun Wang
Chemistry & Biochemistry Faculty Publications
Carbohydrate-based low-molecular-weight gelators are interesting new materials with many potential applications. These compounds can be designed to include multiple stimuli-responsive functional groups. In this study, we designed and synthesized several chemically responsive bola-glycolipids and dimeric carbohydrate- and diarylethene-based photoswitchable derivatives. The dimeric glycolipids formed stable gels in a variety of solvent systems. The best performing gelators in this series contained decanedioic and dithienylethene (DTE) spacers, which formed gels in eight and nine of the tested solvents, respectively. The two new DTE-containing esters possessed interesting photoswitching properties and DTE derivative 7 was found to have versatile gelation properties in many solvents, …
Detection And Quantification Of Antiviral Drug Tenofovir Using Silver Nanoparticles And Surface Enhanced Raman Spectroscopy (Sers) With Spatially Resolved Hotspot Selection,
2023
Old Dominion University
Detection And Quantification Of Antiviral Drug Tenofovir Using Silver Nanoparticles And Surface Enhanced Raman Spectroscopy (Sers) With Spatially Resolved Hotspot Selection, Marguerite R. Butler, Jana Hrncirova, Terry A. Jacot, Sucharita Dutta, Meredith R. Clark, Gustavo F. Doncel, John B. Cooper
Chemistry & Biochemistry Faculty Publications
This study introduces a convenient and ultra-sensitive method of detection and quantification of the antiviral drug, tenofovir (TFV), by surface-enhanced Raman spectroscopy (SERS). Novel spatially resolved instrumentation for spectral acquisition and subsequent statistical analysis for hot spot selection was developed for convenient quantification of TFV in an aqueous matrix. Methods of statistical analysis include the use of partial least squares (PLS) regression vector analysis and spectral ranking by quality indices computed using CHAOS theory. Hydroxylamine-reduced Ag colloidal nanoparticles evaporated to dryness on an aluminum well-plate were used as the SERS substrate. To our knowledge, quantification of TFV down to 25 …
Enhancing The Conformational Stability Of The Cl-Par-4 Tumor Suppressor Via Site-Directed Mutagenesis,
2023
Old Dominion University
Enhancing The Conformational Stability Of The Cl-Par-4 Tumor Suppressor Via Site-Directed Mutagenesis, Samjhana Pandey, Krishna K. Raut, Antoine Baudin, Lamya Djemri, David S. Libich, Komala Ponniah, Steven M. Pascal
Chemistry & Biochemistry Faculty Publications
Intrinsically disordered proteins play important roles in cell signaling, and dysregulation of these proteins is associated with several diseases. Prostate apoptosis response-4 (Par-4), an approximately 40 kilodalton proapoptotic tumor suppressor, is a predominantly intrinsically disordered protein whose downregulation has been observed in various cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) is active and plays a role in tumor suppression by inhibiting cell survival pathways. Here, we employed site-directed mutagenesis to create a cl-Par-4 point mutant (D313K). The expressed and purified D313K protein was characterized using biophysical techniques, and the results were compared to that of the wild-type (WT). We have …
Histidine Enhances The Anticancer Effect Of Gemcitabine Against Pancreatic Cancer Via Disruption Of Amino Acid Homeostasis And Oxidant—Antioxidant Balance,
2023
University of Nebraska Medical Center
Histidine Enhances The Anticancer Effect Of Gemcitabine Against Pancreatic Cancer Via Disruption Of Amino Acid Homeostasis And Oxidant—Antioxidant Balance, Narendra Kumar, Satyanarayana Rachagani, Gopalakrishnan Natarajan, Alexandra Crook, Thiyagarajan Gopal, Vinothkumar Rajamanickam, Jyoti B. Kaushal, Sirpu N. Nagabhishek, Robert Powers, Surinder K. Batra, Viswanathan Saraswathi
Robert Powers Publications
Simple Summary: Amino acid metabolism is aberrantly altered in pancreatic cancer (PC). Evidence suggests that circulating histidine (His) levels are low in PC. However, the role of His in modulating the progression of PC remains unknown. We determined the role of His in altering the therapeutic effectiveness of gemcitabine (Gem) against PC. We provide evidence that the expression of histidine ammonia lyase (HAL), an enzyme involved in His catabolism, is greatly increased in mouse and human pancreatic tumors. We show that combining His with Gem led to enhanced cytotoxic effects against aggressive PC cell lines. Our metabolomics analysis revealed that …
Multiplatform Untargeted Metabolomics,
2023
University of Nebraska-Lincoln
Multiplatform Untargeted Metabolomics, Micah J. Jeppesen, Robert Powers
Robert Powers Publications
Metabolomics samples like human urine or serum contain upwards of a few thousand metabolites, but individual analytical techniques can only characterize a few hundred metabolites at best. The uncertainty in metabolite identification commonly encountered in untargeted metabolomics adds to this low coverage problem. A multiplatform (multiple analytical techniques) approach can improve upon the number of metabolites reliably detected and correctly assigned. This can be further improved by applying synergistic sample preparation along with the use of combinatorial or sequential non-destructive and destructive techniques. Similarly, peak detection and metabolite identification strategies that employ multiple probabilistic approaches have led to better annotation …
Exploring The Complementarity Of Measures Of Instructional Practices,
2023
University of Virginia
Exploring The Complementarity Of Measures Of Instructional Practices, Lu Shi, Robert M. Erdmann, Anthony Pellegrini, Victoria Johnson, Binh Le, Trina Popple, Zachary Nelson, Molly Undersander Gaston, Marilyne Stains
Department of Chemistry: Faculty Publications
The assessment of instructional quality has been and continues to be a desirable, yet difficult endeavor in higher education. The development of new teaching evaluation frameworks along with instruments to measure various aspects of teaching practices holds promise. The challenge rests in the implementation of these frameworks and measures in authentic settings. Part of this challenge is for instructors, researchers, and administrators to parse through and select a meaningful set of tools from the plethora of existing instruments. In this study, we aim to start clarifying the landscape of measures of instructional practice by exploring the complementarity of two existing …
The Discovery And Characterization Of Novel Potent 5-Substituted 3, 3’, 4’, 7-Tetramethoxyflavonoid Dna Triplex Specific Binding Ligands,
2023
University of the Pacific
The Discovery And Characterization Of Novel Potent 5-Substituted 3, 3’, 4’, 7-Tetramethoxyflavonoid Dna Triplex Specific Binding Ligands, Vanessa Marie Rangel
University of the Pacific Theses and Dissertations
Chemotherapy works by killing fast dividing cells. Unfortunately, these drugs are not specific to cancer tissue and can damage normal cells. Chemotherapy is like taking poison and hoping it kills the cancer cells before it kills you. As an alternative, many researchers have investigated the use of antigene therapy to selectively target cancer causing genes to avoid off target effects. Although promising, the theory is limited by the stability of the triplex structure. Here, we report the discovery of potent triplex binding ligands derived from the natural product quercetin. Chemical derivatives of 5-substituted 3, 3’, 4’, 7-tetramethoxyquercetin derivatives were characterized …
Investigating The Interactions Of The Iron-Sulfur Mitochondrial Protein, Mitoneet With Its Binding Partners,
2023
West Virginia University
Investigating The Interactions Of The Iron-Sulfur Mitochondrial Protein, Mitoneet With Its Binding Partners, Ebenezer Osei Newton
Graduate Theses, Dissertations, and Problem Reports (ETD)
MitoNEET belongs to the CDGSH Iron-Sulfur Domain (CISD)-gene family of proteins and is a [2Fe-2S] cluster-containing protein found on the outer membrane of mitochondria. The specific functions of mitoNEET/CISD1 remain to be fully elucidated, but the protein is involved in regulating mitochondrial bioenergetics in several metabolic diseases. Unfortunately, drug discovery efforts targeting mitoNEET to improve metabolic disorders are hampered by the lack of ligand-binding assays for this mitochondrial protein. We have developed a protocol amenable for high-throughput screening (HTS) assay, by modifying an ATP fluorescence polarization method to facilitate drug discovery targeting mitoNEET. Based on our observation that adenosine triphosphate …
Application Of Mass Spectrometry For The Characterization Of Synthetic Oligomers And Natural Lignin,
2023
University of Kentucky
Application Of Mass Spectrometry For The Characterization Of Synthetic Oligomers And Natural Lignin, Poorya Kamali
Theses and Dissertations--Chemistry
As part of the ongoing effort to substitute finite fuel and chemical resources with renewable ones, biomass is emerging as one of the most promising sources. Biomass consists of three main components of cellulose, hemicellulose, and lignin. Traditionally, cellulose has been used extensively in pulping industry, while lignin has been considered waste and is burned to generate heat. Lignin, a complex aromatic polymer component of biomass, has the potential to be used as a source of aromatic chemicals and pharmaceutical synthons. The recalcitrant nature of lignin, the lack of effective lignin breakdown methods and analytical techniques to analyze it are …
Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells,
2023
Eastern Illinois University
Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel
Masters Theses
Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …
Enantioselective Dearomatization Facilitated By Non-Covalent Interactions Of N-Heterocyclic Carbene Catalysts And Pyridinium Salts,
2023
West Virginia University
Enantioselective Dearomatization Facilitated By Non-Covalent Interactions Of N-Heterocyclic Carbene Catalysts And Pyridinium Salts, Jack A. Patterson
Graduate Theses, Dissertations, and Problem Reports (ETD)
Dihydropyridines are a practical organic scaffold commonly used for their pharmaceutical properties. Nucleophilic dearomatization of pyridines has proven to be a useful method in obtaining dihydropyridines. By using N-heterocyclic carbene (NHC) organocatalysts, dihydropyridines can be synthesized with high regioselectivity of the 1,4 regioisomer over the 1,2- regioisomer but often with low enantioselectivity. By incorporating non-covalent interaction contact points, we hypothesize that enantioselectivity can be enhanced. By synthesizing numerous NHCs, each proposed to exhibit a different type of non-covalent interaction (i.e., hydrogen bonding or ion pairing), an understanding of the secondary interactions within this reaction system can be studied and …
Synthesis And Pharmacology Of Illudalic Acid And Analogous Chemical Structures,
2023
West Virginia University
Synthesis And Pharmacology Of Illudalic Acid And Analogous Chemical Structures, Robert Gaston Jr
Graduate Theses, Dissertations, and Problem Reports (ETD)
Natural products are the foundation of modern medicine and an inspiration for chemical innovation. Developing new synthetic strategies to complex natural products drives synthetic innovation and promotes pharmacological exploration. As bioactive secondary metabolites of fungi, illudalic acid and associated analogs have unrealized medicinal potential due to synthetic limitations. Illudalic acid is notably the first selective covalent inhibitor of the LAR-PTPs, a class of enzymes linked to many human illnesses, including stimulant addiction. The chemistry herein focuses on optimizing synthetic routes to illudalic acid and associated analogs toward exploring their pharmaceutical potential. We report a second-generation synthesis of illudinine (55% overall …
2-Aminopyridyl Functionalized Scaffold As A Tool For Systematic Investigation Of B-Glucan Binding And Dectin-1 Activation,
2023
University of Montana
2-Aminopyridyl Functionalized Scaffold As A Tool For Systematic Investigation Of B-Glucan Binding And Dectin-1 Activation, Jasper Alinea Aquino
Graduate Student Theses, Dissertations, & Professional Papers
Tuberculosis (TB) – an infectious disease caused by Mycobacterium tuberculosis (Mtb) – remains an epidemic worldwide contributing to millions of deaths each year. Vaccination is possibly the best means of addressing this global threat. In recent years, synergistic Th1 and Th17 immune responses have emerged as the key players for a vaccine-induced protection against TB. There is currently no vaccine approved for humans that elicits a Th17-mediated immune response. C-Type Lectin Receptors (CLR), specifically Dectin-1, a pattern recognition receptor (PRR) of β-1,3-glucans (β-glucans) primarily from fungi cell walls, is known to induce a Th17-mediated response. The Th17 response upon binding …
Multiomics Approach Captures Hepatic Metabolic Network
Altered By Chronic Ethanol Administration,
2022
University of Nebraska-Lincoln
Multiomics Approach Captures Hepatic Metabolic Network Altered By Chronic Ethanol Administration, Isin Tuna Sakallioglu, Bridget Tripp, Jacy Kubik, Carol A. Casey, Paul G. Thomes, Robert Powers
Department of Chemistry: Faculty Publications
Using a multiplatform and multiomics approach, we identified metabolites, lipids, proteins, and metabolic pathways that were altered in the liver after chronic ethanol administration. A functional enrichment analysis of the multiomics dataset revealed that rats treated with ethanol experienced an increase in hepatic fatty acyl content, which is consistent with an initial development of steatosis. The nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC-MS) metabolomics data revealed that the chronic ethanol exposure selectively modified toxic substances such as an increase in glucuronidation tyramine and benzoyl; and a depletion in cholesterol-conjugated glucuronides. Similarly, the lipidomics results revealed that ethanol …
Uv-Light-Tunable P-/N-Type Chemiresistive Gas Sensors Based
On Quasi-1d Tis3 Nanoribbons: Detection Of Isopropanol At
Ppm Concentrations,
2022
Yuri Gagarin State Technical University of Saratov
Uv-Light-Tunable P-/N-Type Chemiresistive Gas Sensors Based On Quasi-1d Tis3 Nanoribbons: Detection Of Isopropanol At Ppm Concentrations, Victor V. Sysoev, Andrey V. Lashkov, Alexey Lipatov, Ilya A. Plugin, Michael Bruns, Dirk Fuchs, Alexey S. Varezhnikov, Mustahsin Adib, Martin Sommer, Alexander Sinitskii
Department of Chemistry: Faculty Publications
The growing demand of society for gas sensors for energy-efficient environmental sensing stimulates studies of new electronic materials. Here, we investigated quasi-one-dimensional titanium trisulfide (TiS3) crystals for possible applications in chemiresistors and on-chip multisensor arrays. TiS3 nanoribbons were placed as a mat over a multielectrode chip to form an array of chemiresistive gas sensors. These sensors were exposed to isopropanol as a model analyte, which was mixed with air at low concentrations of 1–100 ppm that are below the Occupational Safety and Health Administration (OSHA) permissible exposure limit. The tests were performed at room temperature (RT), as …
Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery,
2022
Kennesaw State University
Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore
Symposium of Student Scholars
Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …
Chapman University
Probing Conformational Landscapes And Mechanisms Of Allosteric Communication In The Functional States Of The Abl Kinase Domain Using Multiscale Simulations And Network-Based Mutational Profiling Of Allosteric Residue Potentials, Keerthi Krishnan, Hao Tian, Peng Tao, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
In the current study, multiscale simulation approaches and dynamic network methods are employed to examine the dynamic and energetic details of conformational landscapes and allosteric interactions in the ABL kinase domain that determine the kinase functions. Using a plethora of synergistic computational approaches, we elucidate how conformational transitions between the active and inactive ABL states can employ allosteric regulatory switches to modulate intramolecular communication networks between the ATP site, the substrate binding region, and the allosteric binding pocket. A perturbation-based network approach that implements mutational profiling of allosteric residue propensities and communications in the ABL states is proposed. Consistent with …
Investigating The Effects Of Ionic Liquids On Dna Gquadruplex And Protein Structure Using Molecular Dynamics Simulations,
2022
Rowan University
Investigating The Effects Of Ionic Liquids On Dna Gquadruplex And Protein Structure Using Molecular Dynamics Simulations, Nicholas J. Paradis
Theses and Dissertations
Nucleic acids and proteins have huge implications in biomedicine and bioengineering, however their storage instability limits their applicability and current storage protocols are expensive and globally-inaccessible. Finding an alternative biocompatible media to store nucleic acids and proteins would reduce costs and increase their applicability. Ionic liquids (ILs) are molten salt compounds that have been shown to modulate the stability and activity of nucleic acids and proteins. In this thesis, molecular modeling studies of DNA/RNA and protein structure in ILs will be discussed (Chapter 1) and this method will be used to study the IL effects on the structure on the …
Design, Synthesis, And Characterization Of Nqo1-Activatable Luminescent Probes,
2022
Louisiana State University and Agricultural and Mechanical College
Design, Synthesis, And Characterization Of Nqo1-Activatable Luminescent Probes, Ovini Vionika Weeratung Kankanamge
LSU Doctoral Dissertations
Being among the top ten causes of death, cancer has constantly been able to grab the attention of researchers all around the world. While several treatment methods prevail to cure cancer, the seriousness of this medical condition requires continuous work in the development of novel treatments as well as scientific advancements in order to achieve early detection of the disease. Luminescence imaging is an emerging field in both diagnosis of diseases, as well as a means to provide guidance in clinical surgeries. While there exist only a few contrasting agents approved by the Food and Drug Administration, the need for …
