Chemistry Commons^™

Strictinin, A Novel Ror1-Inhibitor, Represses Triple Negative Breast Cancer Survival And Migration Via Modulation Of Pi3k/Akt/Gsk3ss Activity., Norman Fultang, Abhinav Illendula, Brian Chen, Chun Wu, Subash C. Jonnalagadda, Nathan Baird, Zachary Klase, Bela Peethambaran

College of Science & Mathematics Departmental Research

Triple Negative Breast Cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by the absence of hormone receptors usually targeted by hormone therapies like Tamoxifen. Because therapy success and survival rates for TNBC lag far behind other breast cancer subtypes, there is significant interest in developing novel anti-TNBC agents that can target TNBC specifically, with minimal effects on non-malignant tissue. To this aim, our study describes the anti-TNBC effect of strictinin, an ellagitanin previously isolated from Myrothamnus flabellifolius. Using various in silico and molecular techniques, we characterized the mechanism of action of strictinin in TNBC. Our results suggest …

Using Green Emitting Ph-Responsive Nanogels To Report Environmental Changes Within Hydrogels: A Nanoprobe For Versatile Sensing, Mingning Zhu, Dongdong Lu, Shanglin Wu, Qing Lian, Wenkai Wang, L. Andrew Lyon, Weiguang Wang, Paulo Bártolo, Brian R. Saunders

Engineering Faculty Articles and Research

Remotely reporting the local environment within hydrogels using inexpensive laboratory techniques has excellent potential to improve our understanding of the nanometer-scale changes that cause macroscopic swelling or deswelling. Whilst photoluminescence (PL) spectroscopy is a popular method for such studies this approach commonly requires bespoke and time-consuming synthesis to attach fluorophores which may leave toxic residues. A promising and more versatile alternative is to use a pre-formed nanogel probe that contains a donor/acceptor pair and then “dope” that into the gel during gel assembly. Here, we introduce green-emitting methacrylic acid-based nanogel probe particles and use them to report the local environment …

The Characterization Of A New Metabolite From A Trichodesmium Bloom, Kelly M. Mcmanus

Senior Honors Projects

Our laboratory has been investigating blooms of Trichodesmium, a genus of ecologically important, nitrogen-fixing cyanobacteria, collected from Padre Island in the Gulf of Mexico. Trichodesmium species are an underexplored biological source of cyanobacteria – a taxa that has been shown to produce chemically diverse secondary metabolites. With our focus on the isolation and structure characterization of new bioactive marine natural products, our research group has discovered over 25 new-to-science compounds over the past three years from these blooms. UV and mass spectrometry-guided isolation of Trichodesmium chromatography fractions were utilized to isolate a new metabolite. Isolation of this metabolite was …

A Pretargeted Spect Imaging Strategy Employing Technetium-99m Based On Bioorthogonal Diels-Alder Click Chemistry, Justin H. Walsh

Dissertations, Theses, and Capstone Projects

A series of related N₃S ^99mTc-peptide complexes were synthesized and tested for use in pretargeting SPECT imaging that utilizes the bioorthogonal Diels-Alder click reaction between tetrazine (Tz) and transcyclooctene (TCO). The objective was to optimize the excretory pathways of the ^99mTc-peptide complexes for maximum tumor targeting with the in vivo “click” and minimum non-target uptake. The ^99mTc–tetrazine constructs were prepared by reaction of ^99mTc-peptide complexes (^99mTc-FKC, ^99mTc-FKCR, ^99mTc-DKC, and ^99mTc-SKC) with Tz-NHS or Tz-PEG₅-NHS to form ^99mTc FK(Tz)C, ^99mTc-FK(PEG₅-Tz)CR, ^99mTc-DK(PEG₅-Tz)C, …

Effect Of Salt Concentration On Electrochemical Detection Of Dna, Ziming Dong, Eddie Madrigal, Ryan West Dr.

Creative Activity and Research Day - CARD

Electrochemical approaches for biological sensing offer the potential advantages of facile sample preparation, fast response times, ease of parallel and multiplexed measurements, and the possibility of miniaturization (of sample sizes, electrodes, and associated electronics). All of these factors contribute towards the feasibility of electrochemical methods in biological sensing and analysis. This potential has already been achieved with the commercialization of blood glucose meters, which often rely on an electrochemical transduction mechanism. We have previously demonstrated the ability to electrochemically detect and differentiate complementary and mismatched DNA using our method of melting DNA duplexes at electrified gold surfaces, i.e. e-melting. Recently, …

Mechanistic Studies And Derivative Effects In 1, 3, 4- Oxadiazole Synthesis Via Cyclodehydration Reactions, Evan Huggins

Undergraduate Honors Thesis Projects

In the world of pharmaceutical synthesis, research to combat foreign pathogens is always necessary. Scientists have been exploring different methods in order to synthesize the most effective compounds in antibacterial, anticancer, anti-inflammatory, and many other treatments. A key component within these versatile compounds are 1,3,4-oxadiazoles. Current methods to synthesize these compounds are inefficient. This research seeks to improve oxadiazole synthesis; however, the mechanism of this reaction is unknown. The goal of this project was to study the mechanistic pathway in the discovered, one-pot cyclodehydration synthesis of 1,3,4-oxadiazoles. In the first part of this study, a diacylhydrazine intermediate was proposed. This …

Mobilization Of Calcium Across Mineralized Tissues In Yellow Perch, Perca Flavescens, Taylor Bopp

Student Scholar Showcase

Bones in many higher teleost fish, such as percids and centrarchids, lack osteocytes that function as both chemo- and mechano-sensors, and thus, are not actively involved in homeostasis of blood calcium level. Nonetheless, the vertebrae of yellow perch, Perca flavescens (P. flavescens), living in darker and low calcium (Ca) water, have demonstrated adaptive modeling and remodeling of vertebrae to be more mineralized and thus enhance transmission of the axial muscle torque into the thrust force for the C-start predator escape behavior. The prey-predator interaction is expected to occur at closer range between prey fish and predator fish in …

Hour-Level Resolution On Consumption Pattern Of Substance Abuse, Jarrett Mauk, Rhiannon Huffines, Brittney Nelson, Tara Croft, Bikram Subedi

Scholars Week

Conventional survey-based approaches of determining the consumption statistics of drugs in communities are suffered from non-response biases, and typically underestimate the actual consumption. Time and cost-intensive conventional approaches, therefore, can’t be utilized to determine high-resolution temporal variability in drug consumption. In this study, the temporal trend of consumption of 10 illicit and 26 prescribed neuropsychiatric drugs was determined at hour-level resolution utilizing wastewater-based epidemiology. The hourly composite raw wastewater (every 10 minutes) samples were collected for three consecutive days in a typical week (total of 72 samples), analyzed for target drug residues using UPLC-MS/MS, and back-calculated the consumption rate of …

Fluoride Removal From Water Using A 3d Printed Calcium Carbonate Filter, Sophia Bakar, David Kahler, Benjamin S. Goldschmidt

Undergraduate Research and Scholarship Symposium

Groundwater containing high concentrations of fluoride is the most common source of drinking water in rural areas in parts of east Africa, India, and China. The elevated levels of fluoride cause skeletal and dental fluorosis, which is the weakening and decay of bone structures due to the leeching of calcium from the body as calcium and fluoride bond by the process of adsorption. Over 150 million people are suffering from some form of fluorosis due to the consumption of groundwater. Calcium carbonate has been demonstrated to influence fluoride removal in several forms. To make fluoride removal a cost-effective and user-friendly …

Ethanolamine Regulates Cqsr Quorum-Sensing Signaling In Vibrio Cholerae, Samit Watve, Kelsey Barrasso, Sarah A. Jung, Kristen J. Davis, Lisa A. Hawver, Atul Khataokar, Ryan G. Palaganas, Matthew B. Neiditch, Lark Perez, Wai-Leung Ng

College of Science & Mathematics Departmental Research

The pathogen that causes cholera, Vibrio cholerae, uses the cell-cell communication process known as quorum sensing (QS) to regulate virulence factor production and biofilm formation in response to changes in population density and complexity. QS is mediated through the detection of extracellular chemical signals called autoinducers. Four histidine kinases, LuxPQ, CqsS, CqsR and VpsS, have been identified as receptors to activate the key QS regulator LuxO at low cell density. At high cell density, detection of autoinducers by these receptors leads to deactivation of LuxO, resulting in population-wide gene expression changes. While the cognate autoinducers that regulate the activity of …

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Synthesis Of A Sulfur Variant For Treatment Of Trypanosomiasis, Carlos Vera-Esquivel

UNO Student Research and Creative Activity Fair

Previous work in our lab has found diphenyl ether benzylamines showed a successful response with a micromolar concentration of our lead compound to treat the deadly Trypanosamiosis rhodesience. Furthermore, mammalian cell lines saw promising resistance towards damages. The goal of this study was to synthesize a diphenyl thio benzylamine variant. This variant was more active toward T. b. rhodesience but showed more toxicity to both rat 10 (IC₅₀ mM) and human cell lines (HFF, HC-₀₄, U-₂ OS, and HEK₂₉₃). The selectivity index (ratio of toxicity to activity in the same concentration units (SI)) …

Pharmacological Aspects Of Resveratrol, Raisa Ramirez, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Resveratrol [(E)-5-(4-hydroxystyryl) benzene-1,3-diol], also known as 3,4′,5-trihydroxystilbene also known as resveratrol is classified as a phytoalexin in plants such as nuts, cocoa, berries and grapes for self-defense against injury and pathogenic attacks by bacteria and fungi. Research on this compound did not gain popularity until the 1990s when a published paper implied the relationship between resveratrol and the decrease in cardiovascular complications due to the consumption of grape fermented wine in French populations. This observation sparked research on resveratrol even though its concentration in wine is relatively low, leading to the realization that resveratrol has potential for benefits in other …

Student-Faculty Collaborative Research Grant Report, Megan Bestwick

Post-Grant Reports

Mitochondria are essential organelles in most eukaryotic cells because of their role in metabolism and the production of ATP by the oxidative phosphorylation (OXPHOS) pathway, as well as other key cellular processes. Metal cofactors, such as copper (Cu) and iron (Fe), are incorporated into OXPHOS protein complexes of yeast located within the inner membrane of the mitochondria. Misincorporation or modulation of these available metals in mitochondrial enzymes leads to the production of reactive oxygen species (ROS). ROS are reactive molecules containing oxygen such as peroxides, superoxide, and hydroxyl radicals. Yeast are a good model for studying aging and the effect …

Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas

Pharmacy Faculty Articles and Research

A series of novel chromone/aza-chromone fused α-aminophosphonate derivatives were synthesized in good yields using silica chloride as the catalyst. All the synthesized compounds were tested for their c-Src kinase inhibitory activity. Aza-chromone compound showed Src kinase inhibition with an IC50 value of 15.8 µM. The compounds were subjected to molecular docking and dynamics simulations to study the atomic level interactions with an unphosphorylated proto-oncogenic tyrosine protein kinase Src (PDB code 1Y57) as well as phosphorylated tyrosine protein kinase Src (PDB code 2H8H). Docking and molecular dynamic results revealed phosphorylated Src tyrosine kinase protein better results than unphosphorylated tyrosine Src kinase …

Amino Alkynylisoquinoline And Alkynylnaphthyridine Compounds Potently Inhibit Acute Myeloid Leukemia Proliferation In Mice, N Naganna, Clement Opuku-Temeng, Eun Yong Choi, Elizabeth Larocque, Elizabeth T. Chang, Brandon A. Carter-Cooper, Modi Wang, Sandra E. Torregrossa-Allen, Bennett D. Elzey, Rena G. Lapidus, Herman Sintim

Department of Chemistry Faculty Publications

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ackground: Acute myeloid leukemia (AML) remains one of the most lethal, rarely cured cancers, despite decades of active development of AML therapeutics. Currently, the 5-year survival of AML patients is about 30% and for elderly patients, the rate drops to b10%. About 30% of AML patients harbor an activating mutation in the tyrosine kinase domain (TKD) of Fms-Like Tyrosine kinase 3 (FLT3) or a FLT3 internal tandem duplication (FLT3-ITD). In- hibitors of FLT3, such as Rydapt that was recently approved by the FDA, have shown good initial response but pa- tients often relapse due to secondary mutations in the …

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

The Relationship Between Rock Climbing And Total Body Strength And Endurance, Madison Gamma, Alexa Bruce, Madison Massey, Ashlee Cordero

The Corinthian

Purpose: The purpose of our study was to assess the relationship between muscular strength and endurance and time to complete a rock wall climb.

Methods: The researchers of this study tested 22 participants ranging from 19-25 years of age. An informed consent and a Physical Activity Readiness Questionnaire (PARQ+) form were completed by each individual before being cleared to participate in this study. Data collection was completed on two separate days. On the first day, participants completed four fitness tests which consisted of a hand grip strength assessment, a 10-repetition maximum (RM) leg press, a flexed arm hang test, and …

Photoassisted Synthesis Of Complex Polyheterocycles Via Esipt-Driven Dearomative Intramolecular Cycloadditions, Dmitry Kuznetsov

Electronic Theses and Dissertations

This research is focused on the development of novel photoassisted synthetic methodologies that provide straightforward access to complex and diverse libraries of polyheterocycles from modularly assembled precursors. All methods are based on the dearomative cycloadditions between two components: (i) o-azaxylylenes, generated by the excited-state intramolecular proton transfer, and (ii) tethered arene groups.

We have demonstrated the synthetic utility of four new photoinduced processes that yield complex products amenable for post-photochemical modifications:

• [4+4] Cycloaddition of o-azaxylylenes to 1,3,4-oxadiazoles with subsequent dinitrogen extrusion. This reaction furnishes compounds outfitted with epoxide fragments, which undergo ring-openings with various nucleophiles; furthermore, the oxidized products …

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …

Therapeutic Delivery Technology And Its Economic Impact, Paul E. Savas Jr.

Senior Honors Theses

Therapeutic delivery technology is a current area of high interest in both university and industrial settings. These technologies are being developed in order to deliver therapeutic agents, such as genes, proteins, and drugs, to patients more efficiently. Nanoscale delivery vehicles have proven to be useful for these applications; these vehicles may either be naturally produced or chemically synthesized. The physical properties of these nanomaterials must be characterized correctly using instrumentation that evaluates their size, morphology, and potential for agglomeration. These technologies represent a high-growth economic area that fosters entrepreneurship and innovation. Because of this innovative spirit, research and economic interest …

A Complete Approach To Predict Biodistribution Of Nanomaterials Within Animal Species From In-Vitro Data, Edward Price

Electronic Theses and Dissertations

Smart drug-design for antibody and nanomaterial-based therapies allows for optimization of drug efficacy and more efficient early-stage pre-clinical trials. The ideal drug must display maximum efficacy at target tissue sites, but to track and predict distribution to these sites, one must have a mechanistic understanding of the kinetics involved with the individual cells of the tissue itself. This process can be tracked through biological simulations coupled with in-vitro approaches, which result in a rapid and efficient in-depth understanding of drug transport within tissue vasculature and cellular environment. As a result, it becomes possible to predict drug biodistribution within live animal …

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …

I3: Isomerization Of Isomer Ions, Krisztián Gabor Torma

University of the Pacific Theses and Dissertations

Photoelectron Photoion Coincidence (PEPICO) spectroscopy is a robust tool for elucidating complex unimolecular dissociation mechanisms and for determining thermochemical and kinetic data of gas-phase ion dissociations with high accuracy. In this work, the dissociative photoionization of two sets of isomeric systems were analyzed with PEPICO: 1) C7H7+ ions of toluene (Tol) and 1,3,5-cycloheptatriene (CHT), and 2) two butyl alcohol isomers, 1-butanol and isobutanol. Threshold dissociative photoionization data on these four molecules of interest were collected on the imaging PEPICO apparatus at the VUV beamline of the Swiss Light Source. Data analysis was aided by ab initio calculations and Rice-Ramsperger-Kassel-Marcus (RRKM) …

Functionality Of Membrane Proteins Overexpressed And Purified From E. Coli Is Highly Dependent Upon The Strain, Khadija Mathieu, Waqas Javed, Sylvain Vallet, Christian Lesterlin, Marie-Pierre Candusso, Feng Ding, Xiaohong Nancy Xu, Christine Ebel, Jean-Michel Jault, Cédric Orelle

Chemistry & Biochemistry Faculty Publications

Overexpression of correctly folded membrane proteins is a fundamental prerequisite for functional and structural studies. One of the most commonly used expression systems for the production of membrane proteins is Escherichia coli. While misfolded proteins typically aggregate and form inclusions bodies, membrane proteins that are addressed to the membrane and extractable by detergents are generally assumed to be properly folded. Accordingly, GFP fusion strategy is often used as a fluorescent proxy to monitor their expression and folding quality. Here we investigated the functionality of two different multidrug ABC transporters, the homodimer BmrA from Bacillus subtilis and the heterodimer PatA/PatB …

Xflow: An Algorithm For Extracting Ion Chromatograms, Mathew M. Gutierrez, Rob Smith

Graduate Student Theses, Dissertations, & Professional Papers

Abstract: Mass spectrometry is a fundamental tool for modern proteomics. The increasing availability of mass spectrometry data paired with the increasing sensitivity and fidelity of the instruments necessitates new and more potent analytical methods. To that end, we have created and present XFlow, a feature detection algorithm for extracting ion chromatograms from MS1 LC-MS data. XFlow is a parameter-free procedurally agnostic feature detection algorithm that utilizes the latent properties of ion chromatograms to resolve them from the surrounding noise present in MS1 data. XFlow is designed to function on either profile or centroided data across different resolutions and instruments. This …

Metabolomic Analysis Of Urine From A Rat Model Relevant To Diabetes Using Nmr, Anna Hart

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Antibacterial Efficacy Of Nanocarriers Designed To Target Pseudomonas Aeruginosa, Anna Mcalpin

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Multidimensional Mass Spectrometry Of Chemonic™ Ccg-6 Nonionic Surfactant With Separation By Polarity And Shape, Charles Johnson

Williams Honors College, Honors Research Projects

Chemonic™ CCG-6 surfactant is a water-soluble poly(ethylene glycol) (PEG) conjugated alkyl glyceride emollient. This surfactant exists as a complex mixture of a glycerol cores conjugated with poly(ethylene glycol) branches (PEGylation) that were partially esterified with caprylic (C8) and capric (C10) acids. These may be esterified on one, two, or all three arms of the glyceride. The architecture of the structures in this mixture was studied using multidimensional mass spectrometry (MS). Mass spectrometry was interfaced with ultra-performance liquid chromatography (UPLC) and ion mobility (IM) separation. The mixture was separated by reversed-phase LC, oligomers of the star-branched polymer were separated according to …