University of Alabama in Huntsville
Western Michigan University
VCU School of Pharmacy, Dept. of Medicinal Chemistry
University of Nebraska-Lincoln
Ursinus College
University of Kentucky
Missouri State University
Liberty University
The Development Of Novel Radioimmunoconjugates For The Pet Imaging And Radioimmunotherapy Of Cancer,
2023
The Graduate Center, City University of New York
The Development Of Novel Radioimmunoconjugates For The Pet Imaging And Radioimmunotherapy Of Cancer, Samantha M. Sarrett
Dissertations, Theses, and Capstone Projects
Antibodies have long played a vital role in nuclear medicine for both the diagnosis and therapy of various malignancies. The role and development of antibodies in nuclear medicine can be broadly separated into three different categories: 1) bioconjugation strategies, 2) immunoPET imaging, and 3) radioimmunotherapy. This dissertation will attempt to comprehensively cover each of these categories through a series of studies, protocols, and reviews. For the bioconjugation strategies, we will describe the development of a novel site-selective bioconjugation strategy using an innovative lysine-targeting reagent, PFP-bisN3, to prepare [89Zr]Zr-SSKDFO-pertuzumab for visualizing HER2+ breast cancer. Further, …
Development Of New Chemical Probes To Delineate The Polyamine Regulation & Molecular Strategies To Unravel Protein Polyamination,
2023
Rowan University
Development Of New Chemical Probes To Delineate The Polyamine Regulation & Molecular Strategies To Unravel Protein Polyamination, Vennela Tulluri
Theses and Dissertations
Polyamines such as putrescine, spermidine, and spermine modulate critical cellular processes, including gene expression and cell proliferation. Cellular polyamine regulation is a complex mechanism controlled by three different proteins: Ornithine decarboxylase (ODC), Antizyme (OAZ), and Antizyme Inhibitor (AZIN). While ODC is directly involved in polyamine biosynthesis, OAZ, and AZIN regulate the ODC activity via protein-protein interactions. The dysregulation of ODC, OAZ, and AZIN leads to elevated polyamines in numerous pathologies, making them attractive targets for controlling polyamine levels. Besides regulating polyamine synthesis, OAZ modulates polyamine transport. However, the precise mechanism remains elusive. In this research, we discuss our approach to …
Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Mathematics, Physics, and Computer Science Faculty Articles and Research
Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …
Structure-Guided Mutagenesis Reveals The Catalytic Residue That Controls The Regiospecificity Of C6-Indole Prenyltransferases,
2023
Chapman University
Structure-Guided Mutagenesis Reveals The Catalytic Residue That Controls The Regiospecificity Of C6-Indole Prenyltransferases, Ahmed R. Aoun, Nagaraju Mupparapu, Diem N. Nguyen, Tae Ho Kim, Christopher M. Nguyen, Zhengfeiyue Pan, Sherif I. Elshahawi
Pharmacy Faculty Articles and Research
Indole is a significant structural moiety and functionalization of the C−H bond in indole-containing molecules expands their chemical space, and modifies their properties and/or activities. Indole prenyltransferases (IPTs) catalyze the direct regiospecific installation of prenyl moieties on indole-derived compounds. IPTs have shown relaxed substrate flexibility enabling them to be used as tools for indole functionalization. However, the mechanism by which certain IPTs target a specific carbon position is not fully understood. Herein, we use structure-guided site-directed mutagenesis, in vitro enzymatic reactions, kinetics and structural-elucidation of analogs to verify the key catalytic residues that control the regiospecificity of all characterized regiospecific …
Anxiety-Like Behavior In C57bl/6j Mice Is Sexually Dimorphic And Altered By Buprenorphine,
2023
University of Tennessee Knoxville
Anxiety-Like Behavior In C57bl/6j Mice Is Sexually Dimorphic And Altered By Buprenorphine, Ohm Sharma
Chancellor’s Honors Program Projects
No abstract provided.
Design And Synthesis Of Peripherally Selective Endocannabinoid Enzyme Inhibitors For Ocular Indications,
2023
Liberty University
Design And Synthesis Of Peripherally Selective Endocannabinoid Enzyme Inhibitors For Ocular Indications, Kezia Reji Thomas
Senior Honors Theses
Peripherally selective compounds have been found to stimulate endocannabinoid receptor activity, which has been observed to have positive physiological effects such as ocular wound healing and inflammation control. The activation of the cannabinoid 1 receptor via binding of the endogenous ligands, anandamide and 2-arachidonoylglycerol, has been indicated to elicit these effects. Both ligands are controlled by two hydrolase enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which can be targeted for therapeutic inhibition. Sulfonamide derivatives of JZL195 containing carbamate functionalities in the southern region of the inhibitor compounds were produced using novel carbamate exchange reactions. Polar functionalities were …
Computational Design And Molecular Modeling Of Morphine Derivatives For Preferential Binding In Inflamed Tissue,
2023
Chapman University
Computational Design And Molecular Modeling Of Morphine Derivatives For Preferential Binding In Inflamed Tissue, Makena Augenstein, Nayiri Alexander, Matthew Gartner
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6–6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to …
Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Mathematics, Physics, and Computer Science Faculty Articles and Research
Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulation. In this study, we embarked on a systematic comparative analysis of the conformational dynamics, electrostatics, protein stability, and allostery in the different functional states of spike trimers for BA.1, BA.2, and BA.2.75 variants. Using efficient and accurate coarse-grained simulations and atomistic reconstruction of the ensembles, we examined the conformational dynamics of the spike trimers that agree with the recent functional studies, suggesting that BA.2.75 trimers are the most stable …
Development And Validation Of A Liquid Chromatography-Tandem Mass Spectrometry Method For The Determination Of Temozolomide In Mouse Brain Tissue,
2023
Cleveland State University
Development And Validation Of A Liquid Chromatography-Tandem Mass Spectrometry Method For The Determination Of Temozolomide In Mouse Brain Tissue, Raghavi Kakarla, Kimberly Yacoub, Rebecca L. Bearden, Aimin Zhou, Sanjib Mukherjee, Frank Y. Shan, Baochuan Guo
Chemistry Faculty Publications
Temozolomide is a Food and Drug Administration-approved anticancer drug that has poor drug delivery via oral or intravenous routes. A potential strategy to combat this problem is investigating alternative routes of administration, requiring quantitation of the drug in the brain tissues by liquid chromatography-mass spectrometry. However, current methods used to extract the drug from brain tissues resulted in poor recovery and substantial matrix effects. Herein, we reported a new two-step extraction method that involves the use of Proteinase K to lyse tumor tissues to efficiently release the drug, followed by ethanol protein precipitation. The extracts were then separated on a …
Virtual And In Vitro Screening Of Natural Products Identifies Indole And Benzene Derivatives As Inhibitors Of Sars-Cov-2 Main Protease (MPro),
2023
Chapman University
Virtual And In Vitro Screening Of Natural Products Identifies Indole And Benzene Derivatives As Inhibitors Of Sars-Cov-2 Main Protease (MPro), Dony Ang, Riley Kendall, Hagop S. Atamian
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with …
Development Of An Lcms Method To Detect And Quantify Curcumin In A Novel Oral Formulation Of Turmeric,
2023
Roseman University of Health Sciences
Development Of An Lcms Method To Detect And Quantify Curcumin In A Novel Oral Formulation Of Turmeric, Brandon Renninger
Annual Research Symposium
No abstract provided.
Synthesis And Analysis Of Novel Troponoid-Based Chemical Probes,
2023
The Graduate Center, City University of New York
Synthesis And Analysis Of Novel Troponoid-Based Chemical Probes, Alex Berkowitz
Dissertations, Theses, and Capstone Projects
Troponoids are a class of non-benzenoid aromatic species featuring a cycloheptatrienone ring and varying degrees of oxygenation. These scaffolds have proven ubiquitous amongst natural products, and have displayed promise as therapeutic agents against a variety of diseases. Herein, we will describe our efforts towards furthering troponoids as potential pharmaceuticals. In Chapter 1, we outline a kojic acid-derived oxidopyrylium cycloaddition/ring-opening method developed in our lab to generate ahydroxytropolones (aHTs). This route was successfully adapted to synthesize a small library of lipophilic aHTs that were proven to be effective against herpes simplex virus-1 (HSV-1) replication, while providing further insight into the mechanism …
Identification And Biosynthetic Study Of The Siderophore Lysochelin In The Biocontrol Agent Lysobacter Enzymogenes,
2023
University of Nebraska-Lincoln
Identification And Biosynthetic Study Of The Siderophore Lysochelin In The Biocontrol Agent Lysobacter Enzymogenes, Amanda Lynn Miller, Shanren Li, Catherine D. Eichhorn, Yongbiao Zheng, Liangcheng Du
Liangcheng Du Publications
Lysobacter is a genus of bacteria emerging as new biocontrol agents in agriculture. Although iron acquisition is essential for the bacteria, no siderophore has been identified from any Lysobacter. Here, we report the identification of the first siderophore, N1,N8-bis(2,3-dihydroxybenzoyl)spermidine (lysochelin), and its biosynthetic gene cluster from Lysobacter enzymogenes. Intriguingly, the deletion of the spermidine biosynthetic gene encoding arginine decarboxylase or SAM decarboxylase eliminated lysochelin and the antifungals, HSAF and its analogues, which are key to the disease control activity and to the survival of Lysobacter under oxidative stresses caused by excess iron. The production of …
The Reversible Low-Temperature Instability Of Human Dj-1
Oxidative States,
2023
University of Nebraska-Lincoln
The Reversible Low-Temperature Instability Of Human Dj-1 Oxidative States, Tessa Andrews, Javier Seravallic, Robert Powers
Robert Powers Publications
DJ-1 is a homodimeric protein that is centrally involved in various human diseases including Parkinson disease (PD). DJ-1 protects against oxidative damage and mitochondrial dysfunction through a homeostatic control of reactive oxygen species (ROS). DJ-1 pathology results from a loss of function, where ROS readily oxidizes a highly conserved and functionally essential cysteine (C106). The over-oxidation of DJ-1 C106 leads to a dynamically destabilized and biologically inactivated protein. An analysis of the structural stability of DJ-1 as a function of oxidative state and temperature may provide further insights into the role the protein plays in PD progression. NMR spectroscopy, circular …
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 …
Progress In 7sk Ribonucleoprotein Structural Biology,
2023
University of Nebraska-Lincoln
Progress In 7sk Ribonucleoprotein Structural Biology, Momodou B. Camara, Amr M. Sobeh, Catherine D. Eichhorn
Faculty Publications -- Chemistry Department
The 7SK ribonucleoprotein (RNP) is a dynamic and multifunctional regulator of RNA Polymerase II (RNAPII) transcription in metazoa. Comprised of the noncoding 7SK RNA, core proteins, and numerous accessory proteins, the most wellknown 7SK RNP function is the sequestration and inactivation of the positive transcription elongation factor b (P-TEFb). More recently, 7SK RNP has been shown to regulate RNAPII transcription through P-TEFb-independent pathways. Due to its fundamental role in cellular function, dysregulation has been linked with human diseases including cancers, heart disease, developmental disorders, and viral infection. Significant advances in 7SK RNP structural biology have improved our understanding of 7SK …
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
Faculty Publications -- Chemistry Department
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 …
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 …
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 …
