Chemicals and Drugs Commons^™

Remotely Controlled Enzyme Behavior Using Localized Thermal Gradients, Sarah Brown

UNO Student Research and Creative Activity Fair

No existing model describes an identified special case of enzyme behavior when directly stimulated with thermal energy via an RF field.

The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Nano-medicine and biotechnology are the future of medical diagnostics and treatment. The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Direct heating of an enzyme vs bulk heating changes the enzyme activity.

I tested how direct transfer of thermal energy changes rates of enzyme reactions. We created samples of enzymes, attached to ferrous (magnetic) nano-particles, and …

Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe

International Journal of Speleology

The emergence of antibiotic resistance is a global health crisis, thus the search for novel antimicrobial compounds has become a continuous necessity. Underexplored and extreme environments, such as cave ecosystems, have been identified as a promising potential source for the discovery of novel microorganisms with novel antimicrobial compounds (AMC). This study presents the first cave microbiological investigation in Sri Lanka, with a special preference for bioprospecting of novel AMC. The cave sediment characterization demonstrated the presence of close to strong acidic conditions (pH 3.1 – 3.3) and thus indicates the possibility of isolating acidophilic microorganisms. Eight cave wall/ceiling fungal strains …

Methylation Of The D2 Dopamine Receptor Affects Binding With The Human Regulatory Proteins Par-4 And Calmodulin, Alexander Bowitch, Ansuman Sahoo, Andrea M. Clark, Christiana Ntangka, Krishna K. Raut, Paul Gollnick, Michael C. Yu, Steven M. Pascal, Sarah E. Walker, Denise M. Ferkey

Chemistry & Biochemistry Faculty Publications

No abstract provided.

Heterocycles In The Treatment Of Neglected Tropical Diseases, Kush K. Maheshwari, Debasish Bandyopadhyay

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

Background: Neglected Tropical Diseases (NTDs) affect a huge population of the world and the majority of the victims belong to the poor community of the developing countries. Until now, the World Health Organization (WHO) has identified 20 tropical diseases as NTDs that must be addressed with high priority. However, many heterocyclic scaffolds have demonstrated potent therapeutic activity against several NTDs.

Objective: There are three major objectives: (1) To discuss the causes, symptoms, and current status of all the 20 NTDs; (2) To explore the available heterocyclic drugs, as well as their mechanisms of action (if known), that are being used …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Experimental And Computational Observations Of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association., Jasmin Federizon, Conrard Giresse Tetsassi Feugmo, Wei-Chiao Huang, Xuedan He, Kazutoyo Miura, Aida Razi, Joaquin Ortega, Mikko Karttunen, Jonathan F Lovell

Chemistry Publications

Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag); however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid …

Adverse Health Effects Of Kratom: An Analysis Of Social Media Data, Abdullah Wahbeh, Tareq Nasralah, Omar El-Gayar, Mohammad A. Al-Ramahi, Ahmed El Noshokaty

Computer Information Systems Faculty Publications (Archived)

This study investigates the adverse healthcare effects associated with the use of kratom. Using machine learning techniques, we analyzed a total of 36,516 users’ posts related to kratom. The results and analysis showed that social media could help identify important insights related to the use of kratom. The sentiment and emotion analyses showed that the kratom experience was negative and largely associated with anger, fear, disgust, and sadness. The results from. topic modeling showed that kratom is associated with a number of healthcare issues such as rashes and itching, urination, constipation, loss of appetite/weight, dry mouth, seizures, nausea, heartburn, dehydration, …

Transcriptional Repressor Protein Based Macrolide Biosensor Development With Improved Sensitivity, Jayani A. Christopher

Graduate Research Posters

Macrolide antibiotics are in high demand for clinical applications. Macrolides are biosynthesized via giant assembly line polyketide synthases (PKS) which are arranged in a modular fashion. Combinatorial biosynthetic methods have been used to produce diversified macrolides by reprograming these modules and modifying tailoring enzymes required for post synthetic modifications. However it is challenging due to the size and complexity of PKSs. To overcome this challenge, new enzymes for macrolide diversification could be obtained by directed evolution where a large number of enzyme variants need to be screened. Therefore it is important to develop high throughput screening methods to identify the …

A Determination Of The Aerosolization Efficiency Of Drugs Of Abuse In A Eutectic Mixture With Nicotine In Electronic Cigarettes, Laerissa Reveil

Master of Science in Forensic Science Directed Research Projects

Electronic cigarettes (e-cigarettes) were originally advertised as an alternative nicotine delivery system to facilitate smoking cessation. However, their popularity for recreational use has increased due to focuses on their trendiness, convenience, and discreteness along with concerns for its use to consume drugs other than nicotine (DOTN). With the adulteration of e-liquids, usually containing nicotine, with other substances, a greater understanding on how DOTN interact with the e-liquid constituents and how they are delivered to the user is necessary. E-liquids were prepared with 50:50 propylene glycol:vegetable glycerin, pure nicotine, pure methadone hydrochloride, and 1:1 methadone hydrochloride:nicotine and aerosolized via an automated …

A Tool For Segmentation Of Secondary Structures In 3d Cryo-Em Density Map Components Using Deep Convolutional Neural Networks, Yongcheng Mu, Salim Sazzed, Maytha Alshammari, Jiangwen Sun, Jing He

Computer Science Faculty Publications

Although cryo-electron microscopy (cryo-EM) has been successfully used to derive atomic structures for many proteins, it is still challenging to derive atomic structures when the resolution of cryo-EM density maps is in the medium resolution range, such as 5–10 Å. Detection of protein secondary structures, such as helices and β-sheets, from cryo-EM density maps provides constraints for deriving atomic structures from such maps. As more deep learning methodologies are being developed for solving various molecular problems, effective tools are needed for users to access them. We have developed an effective software bundle, DeepSSETracer, for the detection of protein secondary structure …

Philippine Medicinal Plants With Potential Immunomodulatory And Anti-Sars-Cov-2 Activities, Fabian M. Dayrit, Armando M. Guidote Jr, Nina Gloriani, Sheriah Laine M. De Paz-Silava, Irene M. Villaseñor, Rene Angelo S. Macahig, Mario A. Tan, John Ross N. Chua, Isidro C. Sia

Chemistry Faculty Publications

Coronavirus disease 2019 (COVID-19) continues to devastate the world’s health and economy, affecting all aspects of life leading to widespread social disruption. Even as several vaccines have been developed, their availability in developing countries is limited and their efficacy against the variants of SARS-CoV-2 (severe acute respiratory syndrome–coronavirus 2) needs to be continuously assessed. The World Health Organization (WHO) has acknowledged that vaccines alone will not overcome the global challenges of COVID-19. Medicinal plants may provide the needed support. Herein, we identify Philippine medicinal plants that possess phytochemicals with potential anti-SARS-CoV-2 activity and/or immunomodulatory properties that may strengthen one’s immune …

Single-Molecule Investigation Of I-Motif Folding And Dynamics In Bioinspired Dna Platforms, Anoja Megalathan

Theses and Dissertations

Although the canonical right-handed B-DNA is the predominant form of DNA in cells, DNA can adopt other secondary structures such as hairpins, G-quadruplexes (G4), and intercalated motifs (i-motif). These secondary structures are typically formed in the regions with repeat sequences. Among many secondary structures DNA can adopt, G-quadruplexes and i-motifs (tetraplex structures formed in the G-rich and C-rich sequences, respectively) caught significant research interest in recent years due to the prevalence of G-rich and C-rich sequences in the human genome. While G-quadruplexes are extensively studied, little is known about i-motifs – especially their formation and stability under cellular environments. For …

Conformational Modulation Of Α-Helical N-Acetylated Α-Synuclein, Ricardo Fernandez

Theses and Dissertations

Human N-acetylated α-synuclein (^NAcαSyn) has long been accepted as an intrinsically disordered protein (IDP) predominantly found in terminal nerve regions in healthy subjects. ^NAcαSyn structural fluidity enables the formation of transient or dynamic assemblies. Some of these assemblies may serve functional, yet undefined purposes. ^NAcαSyn is highly susceptible to the surrounding environment, leading to misfolding under high cytosolic oxidative stress conditions, which in turn assemble in the form of toxic oligomers or amyloid fibrils. These ^NAcαSyn inclusions along with their accretion and migration within neurons, are pathological hallmarks of Parkinson’s disease (PD), dementia, and multiple …

Design, Synthesis, And Anticancer Properties Of Ru(Ii) Complexes With Organometallic, “Expanded” Bipyridine, And O,O’-Chelating Ligands, Raphael Ryan

Theses and Dissertations--Chemistry

Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Interaction Between Genetic Risk Scores For Reduced Pulmonary Function And Smoking, Asthma And Endotoxin, Sinjini Sikdar, Annah B. Wyss, Mi Kyeong Lee, Thanh T. Hoang, Marie Richards, Laura E. Beane Freeman, Christine Parks, Peter S. Thorne, John L. Hankinson, David M. Umbach, Alison Motsinger-Reif, Stephanie J. London

Mathematics & Statistics Faculty Publications

Rationale Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene–environment interactions, but studies are few.

Methods We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case–control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV₁, …

Combining Cryo-Em Density Map And Residue Contact For Protein Secondary Structure Topologies, Maytha Alshammari, Jing He

Computer Science Faculty Publications

Although atomic structures have been determined directly from cryo-EM density maps with high resolutions, current structure determination methods for medium resolution (5 to 10 Å) cryo-EM maps are limited by the availability of structure templates. Secondary structure traces are lines detected from a cryo-EM density map for α-helices and β-strands of a protein. A topology of secondary structures defines the mapping between a set of sequence segments and a set of traces of secondary structures in three-dimensional space. In order to enhance accuracy in ranking secondary structure topologies, we explored a method that combines three sources of information: a set …

Quantifying Anticancer Drug Doxorubicin Binding To Dna Using Optical Tweezers, Zachary Ells

Honors Program Theses and Projects

Doxorubicin is a successful anticancer drug approved for use in the 1970s and is considered to be one of the most effective cancer treatment methods today. Although Doxorubicin has positive survival statistics it has very negative side effects in many cases. Bleeding from the soles of the palms and feet, along with excruciating pain is often exhibited through the administration of this drug. Based on the preliminary findings utilizing optical tweezers we anticipate that this study will provide critical information about the drug binding mechanism. Single molecule biophysics techniques have provided useful insight into the DNA-binding mechanisms of small molecules. …

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

LSU New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells. By …

Carbon Dots As Artificial Peroxidases For Analytical Applications, Shih-Chun Wei, Yang-Wei Lin, Huan-Tsung Chang

Journal of Food and Drug Analysis

Nanozymes have become attractive in analytical and biomedical fields, mainly because of their low cost, long shelf life, and less environmental sensitivity. Particularly, nanozymes formed from nanomaterials having high surface area and rich active sites are interesting since their activities can be tuned through carefully controlling their size, morphology, and surface properties. This review article focuses on preparation of carbon dots (C dots) possessing peroxidase-like activity and their analytical applications. We highlight the important roles of the oxidation states and surface residues of C dots and their nanocomposites with metal, metal oxides, or metal sulfides playing on determining their specificity …

Design And Synthesis Of Novel No-Drug Hybrid Compound And Green Catalytic Activity Evaluation Of Synthesized Silver Nanoparticles-Halloysite Nanocomposite, Majed Abdullah Bajaber

LSU New Orleans Theses and Dissertations

Acetaminophen is a well-known analgesic that can manage pain and reduce fever. SCP-1 is a derivative of acetaminophen that showed significantly reduced hepatotoxicity and nephrotoxicity comparative to acetaminophen. Nitric oxides have been well known to play a key role in a wide variety of physiological and pathophysiological important processes. It was therefore of interest to synthesize a nitric oxide donor linked to SCP-1 that could have enhanced analgesic and antipyretic activity. A furoxan CAS 1609 as NO-donor was synthesized and linked to SCP-1 successfully. The furoxan CAS 1609 was initially synthesized from tetronic acid to give 1,2- dioxime in 86 …

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations and Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

Ethoxylation And Polymerization Of Cardanol Derived Bifunctional Monomers, James Mgaya

Journal of Humanities and Social Sciences

Cardanol and its derivative; 3-(non-8-enyl)phenol (obtained by ethenolysis reaction of cardanol) were ethoxylated via one-pot reaction with urea and ethylene glycol using Na2CO3/ZnO as co-catalysts. The ethoxylates were later methoxycarbonylated using a 1,2-bis(ditertbutylphosphinomethyl)benzene (DTBPMB) modified palladium catalyst to produce ethoxylated bifunctional monomers. Polymerization of these monomers by heating in the presence of a standard polymerization catalyst, Ti(OBu)4, formed oligomers that were plastic-like. Analysis of these oligomers by MALDI-TOF MS indicated the condensation of up to nine monomer units.

Coevolution, Dynamics And Allostery Conspire In Shaping Cooperative Binding And Signal Transmission Of The Sars-Cov-2 Spike Protein With Human Angiotensin-Converting Enzyme 2, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Binding to the host receptor is a critical initial step for the coronavirus SARS-CoV-2 spike protein to enter into target cells and trigger virus transmission. A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. In this work, we performed a comprehensive computational investigation in which sequence analysis and modeling of coevolutionary networks are combined with atomistic molecular simulations and comparative binding free energy analysis of …

Nicotine In Tobacco Product Aerosols: 'It's Deja Vu All Over Again', Anna K. Duell, James F. Pankow, David H. Peyton

Chemistry Faculty Publications and Presentations

Introduction: The distribution of nicotine among its free-base (fb) and protonated forms in aerosolised nicotine affects inhalability. It has been manipulated in tobacco smoke and now in electronic cigarettes by the use of acids to de-freebase nicotine and form ‘nicotine salts’.

Methods: Measurements on electronic cigarette fluids (e-liquids) were carried out to determine (1) the fraction of nicotine in the free-base form (α fb) and (2) the levels of organic acid(s) and nicotine. Samples included JUUL ‘pods’, ‘look-a-like/knock-off’ pods and some bottled ‘nicotine salt’ and ‘non-salt’ e-liquids.

Results: α fb= 0.12 ±0.01 at 40°C (≈ 37°C) for 10 JUUL products, …

Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

In soft matter, thermal energy causes molecules to continuously translate and rotate, even in crowded environments, thereby impacting the spatial organization and function of most molecular assemblies, such as lipid membranes. Directly measuring the orientation and spatial organization of large collections (>3000 molecules μm⁻²) of single molecules with nanoscale resolution remains elusive. In this paper, we utilize SMOLM, single‐molecule orientation localization microscopy, to directly measure the orientation spectra (3D orientation plus “wobble”) of lipophilic probes transiently bound to lipid membranes, revealing that Nile red's (NR) orientation spectra are extremely sensitive to membrane chemical composition. SMOLM images resolve …

Synthesis, Structure Elucidation And Selected Biological Activities Of Ag(I) And Au(I) Complexes Constructed From Thiosemicarbazone And Phosphine Ligands, Syahrina Nur ‘Ain Abdul Halim

Student Works (2020-2029)

New Ag(I) and Au(I) mixed ligand complexes were synthesised using thiosemicarbazone and phosphine in search of a new biologically active compounds. CHN elemental analysis, powder X-ray diffraction (PXRD), single crystal X-ray diffraction as well as several spectroscopic techniques such as FT-IR, Energy-dispersive X-ray (EDX), 1H, 13C, and 31P{1H} NMR were performed to elucidate the structure of these complexes. Elemental analysis suggested that the stoichiometry of the complexes formed by the reaction of Ag nitrate with thiosemicarbazone in the presence of phosphine was indeed 1:2:1 molar ratio, while for the Au to be in 1:1:1 molar ratio. The Ag and Au …

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

Directed Evolution Of Macrocyclic Peptides For Inhibition Of Autophagy, Joshua Gray

Dissertations and Theses (Open Access)

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of …

Drug Delivery In Catheterized Arterial Blood Flow With Atherosclerosis, Saulo Orizaga, Daniel N. Riahi, Jose R. Soto

School of Mathematical & Statistical Sciences Faculty Publications

We study the problem of drug delivery in a catheterized artery in the presence of atherosclerosis. The problem is modeled in the context of a two-phase flow system which consists of red blood cells and blood plasma. The coupled differential equations for fluid (plasma) and particles (red cells) are solved for the relevant quantities in the reasonable limits. The drug delivery problem is modeled with a partial differential equation that is developed in terms of the drug concentration, blood plasma velocity, hematocrit value and the diffusion coefficient of the drug/fluid. A conservative-implicit finite difference scheme is develop in order to …