Chemistry Commons^™

Late-Stage Functionalization Through Click Chemistry Provides Glut5-Targeting Glycoconjugate As A Potential Pet Imaging Probe, Adelina Oronova, Marina Tanasova

Michigan Tech Publications

The targeting of facilitative sugar transporters (GLUTs) has been utilized in the development of tools for diagnostics and therapy. The interest in this area is promoted by the phenomenon of alterations in cellular metabolic processes that are linked to multitudes of metabolic disorders and diseases. However, nonspecific targeting (e.g., glucose-transporting GLUTs) leads to a lack of disease detection efficiency. Among GLUTs, GLUT5 stands out as a prominent target for developing specific molecular tools due to its association with metabolic diseases, including cancer. This work reports a non-radiolabeled fluoride (19F) coumarin-based glycoconjugate of 2,5-anhydro-D-mannitol as a potential PET imaging probe that …

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Speciated Isotope Dilution Mass Spectrometry In Combination With Thor’S Hammer Metaspike Technology For The Assessment Of Low-Level Biomarkers For Human Health Evaluation, Ashley Ebert

Electronic Theses and Dissertations

Our research team has been focused on quantifying important biological analytes in human blood samples to delineate the biochemical processes underlying certain states of dysfunction and evaluate treatment efficacy. These efforts have been guided by laboratory measurements with the input of medical experts. Speciated isotope dilution mass spectrometry (SIDMS) explained in detail in EPA Method 6800 has been successfully applied in the quantification of an important biomarker analyte for immune function and detoxification processes: glutathione. Past research has proven the molecule a biomarker for autism spectrum disorder (ASD) in the form of the reduced/oxidized glutathione (GSH/GSSG) ratio, and literature has …

An Imaging Mass Spectrometry Investigation Into The N-Linked Glycosylation Landscape Of Pancreatic Ductal Adenocarcinoma And The Development Of Associated Tools For Enhanced Glycan Separation And Characterization, Colin Mcdowell

MUSC Theses and Dissertations

The severity of pancreatic ductal adenocarcinoma (PDAC) is largely attributed to a failure to detect the disease before metastatic spread has occurred. CA19-9, a carbohydrate biomarker, is used clinically to surveille disease progression, but due to specificity challenges is not suitable for early discovery. As CA19-9 and other prospective markers are glycan epitopes, there is great clinical interest in understanding the glycobiology of pancreatic cancer. Unfortunately, few studies have been able to link glycosylation changes directly to pancreatic tumors and instead have focused on peripheral glycan alterations in the serum of PDAC patients. To address this gap in our understanding, …

Groundwater Remediation Using Modified Biochar, Kers Ung-Watson, Ismail Abdulraheem, Nikki Tibayan, Suraj Pochampally

Undergraduate Research Symposium Posters

Biochar, a lightweight black residue made of carbon, has proved to be an effective adsorbent to remove TCE from groundwater. Not only is it an economical substitute for conventional adsorbents but it can be created by using a variety of organic materials. For this project, it will rely on walnut shell feedstock to create biochar as this had the best ability to adsorb TCE.

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 …

A Human Oral Fluid Assay For D- And L- Isomer Detection Of Amphetamine And Methamphetamine Using Liquid-Liquid Extraction, Brian Robbins, Rob E. Carpenter, Mary Long, Jacob Perry

Human Resource Development Faculty Publications and Presentations

Medical providers are increasingly confronted with clinical decision-making that involves (meth)amphetamines. And clinical laboratories need a sensitive, efficient assay for routine assessment of D- and L-isomers to determine the probable source of these potentially illicit analytes. This paper presents a validated method of D- and L-isomer detection in human oral fluid from an extract used for determination of a large oral fluid assay (63 analytes) on an older AB SCIEX 4000 instrument. Taken from the positive extract, D- and L-analytes were added. The method for extraction included addition of internal standard and a 2-step …

Intra-Skeletal Variation In Stable Isotopes Through Non-Destructive Approaches: Applications Of The Patterns Of Skeletal Remodeling To Biological Anthropology, Armando Anzellini

Doctoral Dissertations

Stable isotope analysis is a well-established method in biological anthropology used to deliver data on residence, diet, and life history. Samples for these analyses are often collected from the diaphyses of long bones with an assumption of an expected rate of turnover between five and ten years, depending on the skeletal element. However, the biological foundations of this assumption are still uncertain, especially concerning the intra-skeletal and intra-element variation of isotopic signatures that may relate to patterns of remodeling. Exploring these gaps in intra-element isotopic variation requires fine-grained work using multiple bones from multiple individuals, but such work is limited …

Alpha, Beta-Unsaturated Aldehydes: The Underrepresented Markers Of Disease., Saurin Sutaria

Electronic Theses and Dissertations

The peroxidation of unsaturated fatty acids is a widely recognized metabolic process that creates a complex mixture of volatile organic compounds including aldehydes. Elevated levels of reactive oxygen species in cancer cells promote random lipid peroxidation, which leads to an increase in a variety of aldehydes. Many of these volatile aldehydes are exhaled and are of interest as potential markers of disease. Chapter 1 presents a review of reported aldehydes in the exhaled breath of lung cancer patients. alpha,beta-Unsaturated aldehydes, detected primarily when derivatized during exhaled breath preconcentration, are underreported in the reviewed articles. Chapter 1 concludes with our hypothesis …

Rapid Detection Of Recurrent Non-Muscle Invasive Bladder Cancer In Urine Using Atr-Ftir Technology, Abdullah I. El-Falouji, Dalia M. Sabri, Naira M. Lofti, Doaa M. Medany, Samar A. Mohamed, Mai Alaa-Eldin, Amr Mounir Selim, Asmaa A. El Leithy, Haitham F. Kalil, Ahmed El-Tobgy, Ahmed Mohamed

Chemistry Faculty Publications

Non-muscle Invasive Bladder Cancer (NMIBC) accounts for 80% of all bladder cancers. Although it is mostly low-grade tumors, its high recurrence rate necessitates three-times-monthly follow-ups and cystoscopy examinations to detect and prevent its progression. A rapid liquid biopsy-based assay is needed to improve detection and reduce complications from invasive cystoscopy. Here, we present a rapid spectroscopic method to detect the recurrence of NMIBC in urine. Urine samples from previously-diagnosed NMIBC patients (n = 62) were collected during their follow-up visits before cystoscopy examination. Cystoscopy results were recorded (41 cancer-free and 21 recurrence) and attenuated total refraction Fourier transform infrared (ATR-FTIR) …

A Molecular Chemodosimeter To Probe “Closed Shell” Ions In Kidney Cells, Rashid Mia

Faculty Publications

Two quinidine-functionalized coumarin molecular probes have been synthesized and have been found to bind metal cations (Cd2+, Co2+, Cu2+, Fe2+, Hg2+, Ni2+, and Zn2+) with high affinity in organic–aqueous media (DMSO–HEPES). The chemodosimeters coordinate with the Zn2+ ions in a two-to-one ratio (molecular probe : Zn2+) with a log β of 10.0 M−2. Upon the addition of the closed-shell metal ions studied, a fluorescence turn-on via an excimer formation is seen at 542 nm due to the quinaldine moiety adopting a syn arrangement when coordinated to the metal Zn2+ ions. Confocal microscopy monitored free Zn2+ ions in the Human Embryonic …

Validation Of A Method For Pantoprazole And Its Sulfone Metabolite In Goat Plasma Using High Performance Liquid Chromatography, Sherry Cox, Lainey Harvill, Sarah Bullock, Joseph Smith, Joan Bergman

Faculty Publications and Other Works -- Large Animal Clinical Sciences

No abstract provided.

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Effects Of Cannabinoids On Ligand-Gated Ion Channels, Murat Oz, Keun-Hang Susan Yang, Mohamed Omer Mahgoub

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytocannabinoids such as Δ⁹-tetrahydrocannabinol and cannabidiol, endocannabinoids such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol, and synthetic cannabinoids such as CP47,497 and JWH-018 constitute major groups of structurally diverse cannabinoids. Along with these cannabinoids, CB1 and CB2 cannabinoid receptors and enzymes involved in synthesis and degradation of endocannabinoids comprise the major components of the cannabinoid system. Although, cannabinoid receptors are known to be involved in anti-convulsant, anti-nociceptive, anti-psychotic, anti-emetic, and anti-oxidant effects of cannabinoids, in recent years, an increasing number of studies suggest that, at pharmacologically relevant concentrations, these compounds interact with several molecular targets including G-protein coupled receptors, ion …

The Effects Of Human Behavioral Changes Due To The Covid-19 Pandemic On The Reservoir Of Lytic Escherichia Coli And Staphylococcus Aureus Bacteriophage On Humans At A South Carolina University, Korinne M. Swanson, Owen R. Smith, Paul E. Richardson

Journal of the South Carolina Academy of Science

Bacteriophages are viruses, whose unique ability to infect and lyse bacterial cells may provide valuable insight for evading the repercussions of a post-antibiotic era in medicine. This study isolated and characterized Escherichia coli and Staphylococcus aureus bacteriophage on students and faculty at Coastal Carolina University as a means to understand the viability of human bacteriophage reservoirs for bacteriophage therapy. From September 2021 to March 2022, nasal and postauricular swab samples and a behavioral survey were collected from ninety-three randomly selected participants. Additionally, sixteen participants contributed nasal and postauricular swab samples and a behavioral survey on a monthly basis in a …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Environmental Bacteriophage Detection On Coastal Carolina University Campus, Madison Gentilo, Hailey Oldfield, Gavin Ockert, Paul E. Richardson

Journal of the South Carolina Academy of Science

Bacteriophages are viruses that infect bacteria. These viruses are found ubiquitously in the environment and are more abundant than any living organism on Earth, including bacteria. Eleven sites are designated for weekly sample collection on the campus of Coastal Carolina University. Water samples are filtered and amplified using strains of E. coli B and E. coli K12 to allow potential coliphages in the sample to proliferate to detectable levels. Plaque assays are used as a microbial screen for the presence of bacteriophage. Samples that test positively using the microbial test are analyzed through a molecular test using PCR to identify …

2022 Scas Annual Meeting Program And Bulletin

Journal of the South Carolina Academy of Science

No abstract provided.

3,6-Dimethoxyxanthone From 2,2’,4,4’- Tetrahydroxy-Benzophenone Via Microwave-Assisted Annulation, Sarah E. Knisely, Faith R. Rosario, Salem F. Gebeyehu, Paige E. Heiple, Robert E. Lee Sr

Journal of the South Carolina Academy of Science

Xanthones are tricyclic aromatic compounds that have multiple pharmacological uses due to their anti-tumor, antioxidant, anti-inflammatory, anti-bacterial, and potentially chemopreventive properties. The target of this research was to optimize a two-step synthesis of 3,6-dimethoxyxanthone (3) from 2,2’,4,4’-tetrahydroxy-benzophenone (1) via microwave-assisted (200 °C, 30-40 min., 150 W) sodium acetate-catalyzed annulation. The product, 3,6-dihydroxyxanthone (2), was then methylated to (3) using dimethyl sulfate (DMS) and sodium carbonate in acetone at reflux. The product yields were 93% (>99% purity) for (2) and 94% (>99% purity) for (3). Characterization was accomplished using ¹H NMR, FTIR, melting point, TLC, HPLC, and GCMS. …

Probing Mechanisms Of Binding And Allostery In The Sars-Cov-2 Spike Omicron Variant Complexes With The Host Receptor: Revealing Functional Roles Of The Binding Hotspots In Mediating Epistatic Effects And Communication With Allosteric Pockets, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we performed all-atom MD simulations of RBD–ACE2 complexes for BA.1, BA.1.1, BA.2, and BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD–ACE2 binding interfaces and analysis of electrostatic effects. The binding free energy computations of the Omicron RBD–ACE2 complexes and comprehensive examination of the electrostatic interactions quantify the driving forces of binding and provide new insights into energetic mechanisms underlying evolutionary differences between Omicron variants. A systematic mutational scanning of the RBD residues determines the protein stability centers and binding energy hotpots in the Omicron RBD–ACE2 complexes. By employing the ensemble-based global network analysis, we …

Interpretable Machine Learning Models For Molecular Design Of Tyrosine Kinase Inhibitors Using Variational Autoencoders And Perturbation-Based Approach Of Chemical Space Exploration, Keerthi Krishnan, Ryan Kassab, Steve Agajanian, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In the current study, we introduce an integrative machine learning strategy for the autonomous molecular design of protein kinase inhibitors using variational autoencoders and a novel cluster-based perturbation approach for exploration of the chemical latent space. The proposed strategy combines autoencoder-based embedding of small molecules with a cluster-based perturbation approach for efficient navigation of the latent space and a feature-based kinase inhibition likelihood classifier that guides optimization of the molecular properties and targeted molecular design. In the proposed generative approach, molecules sharing similar structures tend to cluster in the latent space, and interpolating between two molecules in the latent space …

Wastewater-Informed Public Health Intervention Playbook

Sustain Magazine

As the SARS-CoV-2 pandemic quickly spread from country to country and continent to continent in 2020, governments and scientists needed a way to track COVID-19 through populations in order to position public health interventions in the most impactful locations. Having a decision-based risk framework may help to guide policy creation that could minimize or prevent possible outbreaks and surges of infection within communities. The University of Louisville in partnership with Louisville’s Department of Public Health and Wellness tested this strategy in 2021 and 2022. This Wastewater-Informed Public Health Intervention Playbook describes the decisions and actions of that academic and public …

Tetrahydrocurcumin Improves Lipopolysaccharide-Induced Myocardial Dysfunction By Inhibiting Oxidative Stress And Inflammation Via Jnk/Erk Signaling Pathway Regulation, Hanzhao Zhu, Liyun Zhang, Hao Jia, Lu Xu, Yu Cao, Mengen Zhai, Kaifeng Li, Lin Xia, Liqing Jiang, Xiang Li, Yenong Zhou, Jincheng Liu, Shiqiang Yu, Weixun Duan

Chemistry Undergraduate Publications

Background

Acute myocardial dysfunction in patients with sepsis is attributed to oxidative stress, inflammation, and cardiomyocyte loss; however, specific drugs for its prevention are still lacking. Tetrahydrocurcumin (THC) has been proven to contribute to the prevention of various cardiovascular diseases by decreasing oxidative stress and inflammation. This study was performed to investigate the functions and mechanism of action of THC in septic cardiomyopathy.

Methods

After the oral administration of THC (120 mg/kg) for 5 consecutive days, a mouse model of sepsis was established via intraperitoneal lipopolysaccharide (LPS, 10 mg/kg) injection. Following this, cardiac function was assessed, pathological section staining was …

Synthesis And Characterization Of D5-Barbarin For Use In Barbarin-Related Research, Sucheta Kudrimoti, Jacob Machin, Adedamola S. Arojojoye, Samuel G. Awuah, Rodney Eisenberg, Clara Fenger, George Maylin, Andreas F. Lehner, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d₅-barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D₅-barbarin synthesis commenced with production of d₅-2-oxo-2-phenylacetaldehyde oxime (d₅-oxime) from d₅-acetophenone via butylnitrite in an ethoxide/ethanol solution. This d₅-oxime was then reduced with lithium aluminum …

Subtype-Selective Positive Modulation Of KCa2.3 Channels Increases Cilia Length, Young-Woo Nam, Rajasekharreddy Pala, Naglaa Salem El-Sayed, Denisse Laren-Henriquez, Farideh Amirrad, Grace Yang, Mohammad Asikur Rahman, Razan Orfali, Myles Downey, Keykavous Parang, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium (K_Ca2.x) channels are gated exclusively by intracellular Ca²⁺. The activation of K_Ca2.3 channels induces hyperpolarization, which augments Ca²⁺ signaling in endothelial cells. Cilia are specialized Ca²⁺ signaling compartments. Here, we identified compound 4 that potentiates human K_Ca2.3 channels selectively. The subtype selectivity of compound 4 for human K_Ca2.3 over rat K_Ca2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of K_Ca2.3 channels by compound 4 increased flow-induced Ca²⁺ signaling and cilia length, while negative …

Identification And Quantitation Of Unspecified Impurities Discovered In Novel Oral Irinotecan By Lc-Ms/Ms And Uhplc, Laura B. Miller

Forensic Science Master's Projects

Irinotecan is a cancer medication approved for medical use in the United States in 1996. It is currently administered via intravenous injection. However, intravenous dosing has disadvantages such as requirement of administration by a trained professional in a medical facility, possible severe adverse effects, pain at the injection site, and possible hemolysis if injected too rapidly. Previously oral administration was not feasible because the p-glycoprotein (p-GP) on the cell membrane of stomach cells acts as a defense mechanism against harmful substances by pumping the irinotecan back into the intestinal lumen for excretion. With the discovery of the p-GP inhibitor encequidar …

Radioluminescence Based Biochemical Sensing And Imaging Strategies To Measure Local Drug Release And Ph, Gretchen B. Schober

All Dissertations

In this dissertation we describe methods for measuring infection relevant biochemical analytes using radioluminescent and ultrasound luminescent materials. Films and nanoparticles fabricated with europium doped gadolinium oxysulfide (Gd₂O₂S:Eu³⁺) are used to quantitatively measure radiolabeled pharmaceutical concentration, specifically tritium labeled vancomycin (³H-vancomycin). Europium and dysprosium doped strontium aluminate is used to fabricate an ultrasound modulated, pH sensing film. These methods are indicated for theranostic evaluation of implant associated infection. Bacterial biofilms are inherently resistant to traditional antibiotic treatment and can coat biomedical implants. These biofilm related infections are difficult or impossible to eradicate …

Sar Study Of Niclosamide Derivatives In The Human Glioblastoma U-87 Mg Cells, Shizue Mito, Benxu Cheng, Benjamin A. Garcia, Daniela Gonzalez, Xin Yee Ooi, Tess C. Ruiz, Francisco Xavier Elisarraras, Andrew Tsin, Sue Anne Chew, Marco A. Arriaga

Chemistry Faculty Publications and Presentations

Glioblastoma is a lethal malignant brain tumor, and the development of efficient chemotherapeutic agents remains an urgent need. Niclosamide, an anthelmintic drug, which has been used to treat tapeworm infections more than 50 years, has recently attracted renewed attention due to its evident anticancer activities. It has been shown that niclosamide induces cytotoxicity in human glioblastoma U-87 MG cells corresponding with increased protein ubiquitination, ER stress, and autophagy. Furthermore, niclosamide showed down regulation of multiple pro-survival signaling pathways including Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and STAT3, which further caused reduction of U87-MG cell viability. However, the molecular mechanisms of niclosimide and its …

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.