Chemistry Commons^™

Here, There, And Everywhere: Probing Ubiquitin-Cavitand Binding Via 15n-1h Hsqc, Julia Didziulis

Scripps Senior Theses

Ubiquitination and other post-translational modifications play a major role in the proliferation of many neurodegenerative diseases, developmental disorders, and cancers, and as such are subjects of recently increased biochemical interest. Expanding upon such research, this study confirmed a robust method of ubiquitin expression and purification, then used 15N-1H HSQC to analyze ubiquitin samples containing varying concentrations of a deep cavitand with affinity for lysine and arginine side chains. In the pure ubiquitin spectrum, arginine side chain chemical shifts were detected in the nitrogen 80-85 ppm range and lysine side chain signals were undetected. However, upon introduction of the cavitand, collection …

Sequential Block Copolymers Of Polyisobutylene And Polyolefins, Manwel Labib

Williams Honors College, Honors Research Projects

A two-step approach will be utilized to synthesize random polyolefin multiblock-copolymers. This strategy takes advantage of a,w-terminated telechelic polyolefins. Polypropylene (iPP)/polyethylene (PE) are picked because of their strength, and polyisobutylene (PIB) because of its hemocompatibility. This copolymer is theorized to make for robust bio-inert plastic, which can be used for surgical mesh implants.

Determining The Effects Of Chemical Exposure On Hepatocyte Mitochondrial Networks And Cell Viability, Bethany Eaton

All Master's Theses

Mitochondria are cellular organelles that are becoming more recently studied. One of their main functions is the production of energy through cellular respiration, which is crucial to cell life. However, they are also associated with numerous disease states. It is hypothesized that reactive oxygen species (ROS), largely produced in mitochondria, induce oxidative stress and affect mitochondrial morphology along with cell viability. This study compares chemical exposure of menadione, an ROS producer, and phthalates (plasticizers) on two mouse hepatocyte cell lines to determine the effects they have on mitochondrial morphology and cell viability. Three experiments were performed to analyze the effects …

Synthesis Of Rna Nucleotides Under Probable Prebiotic Conditions, Ryan Stimson

Williams Honors College, Honors Research Projects

RNA being composed of multiple covalently linked nucleotides is thought to have been a precursor to life circa 4.3-3.8 billion years ago. Non-enzymatically formed adenosine monophosphate (AMP), more specifically, is a vitally important subtopic of the self-assembly of the first RNA sequence. The goal of this study was to synthesize AMP non-enzymatically under benign conditions that are likely to have existed on early Earth. In this experiment, 3’,5’-cAMP was successfully formed using wet-dry cycles at 80°C paired with the minerals zeolite beta, hydroxyapatite, and aerosil 300 in the presence of adenosine, urea, and pyrophosphate. A nuclear magnetic resonance spectrometer was …

The Influence Of Hydrogen Peroxide On The Enrichment Of Fe(Iii) Reducing Bacteria From Acid Mine Drainage, Susami Seth

Williams Honors College, Honors Research Projects

It is hypothesized that the ocean of Europa, a Jupiter moon, hosts bacteria on its oceanic floor. Understanding how Fe(III) reducing bacteria (FeRB) from AMD utilize organic materials within its surrounding environment outlines how FeRB could thrive and tolerate extreme conditions. FeRB are known to tolerate metals and highly reactive oxidants species (ROS), but in this experiment, H₂O₂ was the experimental factor to further test FeRB tolerance. H₂O₂ is a common ROS and is damaging to living material such as proteins, DNA, and RNA. A range of H₂O₂ concentrations were fed …

Multilevel Computational Investigation Into The Dynamics And Reaction Mechanisms Of Non-Heme Iron And 2-Oxoglutarate Dependent Enzymes, Shobhit Sanjeev Chaturvedi

Dissertations, Master's Theses and Master's Reports

Computational chemistry methods have been extensively applied to investigate biological systems. This dissertation utilizes a multilevel computational approach to explore the dynamics and reaction mechanisms of two groups of enzymes belonging to non-heme Fe(II) and 2-oxoglutarate (2OG) dependent superfamily – histone lysine demethylases from class 7 and ethylene forming enzyme (EFE). Chapter 2 uncovers the role of conformational dynamics in the substrate selectivity of histone lysine demethylases 7A and 7B. The molecular dynamics (MD) simulations of the two enzymes revealed the importance of linker flexibility and dynamics in relative orientations of the reader (PHD) and the catalytic (JmjC) domains. Chapter …

Nonhematopoietic Erythropoietin: A Study Of Signaling, Structure, And Behavior, Nicholas John Pekas

Dissertations and Theses

Erythropoietin (EPO) is a cytokine hormone known for initiating red blood cell proliferation by binding to its homodimer receptor (EPOR)2 in the bone marrow. Recent progress in neurobiology has shown that EPO also exerts robust neurotrophic and neuroprotective activity in the CNS. It is widely thought that EPO’s neurotrophic activity is centrally involved in its antidepressant and cognitive enhancing effects. However, EPO’s potent erythropoietic effects prevent it from being used in the clinic to treat psychiatric disorders. A chemically engineered non-erythropoietic derivative of EPO, carbamoylated EPO (CEPO), produces psychoactive effects without activating hematopoiesis. However, CEPO is expensive to produce and …

Copper(Ii) And Silver(I)‑1,10‑Phenanthroline‑5,6‑Dione Complexes Interact With Double‑Stranded Dna: Further Evidence Of Their Apparent Multi‑Modal Activity Towards Pseudomonas Aeruginosa, Anna Clara Milesi Galdino, Lívia Viganor, Matheus Mendonça Pereira, Michael Devereux, Malachy Mccann, Marta Helena Branquinha, Zara Molphy, Sinéad O'Carroll, Conor Bain, Georgia Menounou, Andrew Kellett, André Luis Souza Dos Santos

Articles

Tackling microbial resistance requires continuous efforts for the development of new molecules with novel mechanisms of action and potent antimicrobial activity. Our group has previously identified metal-based compounds, [Ag(1,10-phenanthroline-5,6-dione)2]ClO4 (Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)3](ClO4)2.4H2O (Cu-phendione), with efficient antimicrobial action against multidrug-resistant species. Herein, we investigated the ability of Ag-phendione and Cu-phendione to bind with double-stranded DNA using a combination of in silico and in vitro approaches. Molecular docking revealed that both phendione derivatives can interact with the DNA by hydrogen bonding, hydrophobic and electrostatic interactions. Cu-phendione exhibited the highest binding affinity to either major (− 7.9 kcal/mol) or minor (− 7.2 kcal/mol) …

Review Of The Effects Of Asphalt Fume Emission (Vocs And Pahs) In Vitro, In Vivo And Human Studies, Omran Taqi, Nastassja Lewinski, Elham Fini, Eran Rozewski, Judith Klein-Seetharaman

Undergraduate Research Posters

Review of the effects of Asphalt fume emission (VOCs and PAHs) in vitro, in vivo and human studies

Omran Taqi, Nastassja Lewinski¹

1) Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA

Background

Asphalt is abundantly available around human operations including road paving and roofing sites. However, their emissions and fumes (specifically volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs)) have been found to have adverse effects on health. Asphalt fumes are a class 2A carcinogen and exposure can increase the risk of lung cancer, asthma, headache, fatigue, and other cardiovascular diseases.

Methods

We used …

Synthesis Of 6,6- And 7,7-Difluoro-1-Acetamidopyrrolizidines And Their Oxidation Catalyzed By The Nonheme Fe Oxygenase Lolo, Nabin Panth

Theses and Dissertations--Chemistry

One of the remarkable steps in loline alkaloid biosynthesis is the installation of an ether bridge between two unactivated C atoms in 1-exo-acetamidopyrrolizidine (AcAP). LolO, a 2-oxoglutarate-dependent nonheme Fe oxygenase, catalyzes both the hydroxylation of AcAP and the resulting alcohol's cycloetherification to give N-acetylnornoline (NANL). The mechanism of hydroxylation is well understood, but the mechanism of the oxacyclization is not. I synthesized difluorinated analogs of AcAP in an attempt to further understand the mechanism of the unusual cycloetherification step.

I prepared 6,6-F₂-AcAP in eight steps from N,O-protected 4-oxoproline. The key step was a Dieckmann …

The Role Of Charge On Dna Packaging And Integrity Within Reconstituted Peptide-Dna Assemblies, Ehigbai Oikeh

Theses and Dissertations--Chemistry

In nature, DNA exists primarily in a highly compacted form. The compaction of DNA in vivo is mediated by cationic proteins; histone in somatic nuclei and arginine-rich peptides called protamines in sperm chromatin. The packaging in the sperm nucleus is significantly higher than somatic nuclei resulting in a final volume roughly 1/20^th that of a somatic nucleus. This tight packaging results in a near crystalline packaging of the DNA helices. While the dense packaging of DNA in sperm nuclei is considered essential for both efficient genetic delivery as well as DNA protection against damage by mutagens and oxidative species, …

Development Of Fluorescence Based Approaches To Understand Astrocyte Biology In The Context Of Nicotine And Nicotinic Receptor Activity, Surya P. Aryal

Theses and Dissertations--Chemistry

Smoking and tobacco use (STU) is a major global health problem and worldwide more than six million people die due to tobacco related diseases each year. Although majority of smokers try to quit smoking several times in their life, traditional therapeutic approaches, which focus only on neuronal cells, have a very low success rate. Understanding the effect of nicotine on glial cells, synaptic communication and blood vasculature in the brain can provide further insights on the neurobiology of substance abuse and can potentially help to design better therapeutic approaches. Glial cells are non-excitable cells in the brain which do not …

Design And Synthesis Of Purine Based Neuroprotectors And Novel Synthetic Methods For The Trifluoromethylation Of Aldehyde Hydrazones, Puspa Aryal

Doctoral Dissertations

"Purine-derived compounds are widely investigated as cyclin-dependent kinase inhibitors that have broad applications in the design of pharmaceuticals for treating diseases, such as diabetes, atherosclerosis, and cancers. Towards the goal of effective AGE-inhibitors, and neuroprotector compounds we have synthesized a series of novel purine-based triazoles and investigated their neuroprotective effects, using SHSY-3Y human neuroblastoma cell line. Through these studies, we have identified purine-based neuroprotector compounds that favorably modulate oxidative stress induced by the Fenton reaction-generated reactive oxygen species (ROS).

The C(sp²−H)-trifluoromethylation of hydrazones would give access to the αtrifluoromethylated hydrazones that can serve as intermediates in the synthesis …

Bodipy Based Photodynamic Therapy And Potassium Probes, Xiangshan Liu

Dissertations

Boron dipyrromethene (BODIPY) has become more and more popular in photophysical and biological applications. BODIPY based fluorescence compounds have numerous advantage properties including low toxicity, high absorption extinction coefficients, high fluorescence quantum yields, sharp fluorescence emissions, and resistance to photobleaching. All the good properties lead to the wide applications of BODIPY based compounds. In this research, two different kinds of BODIPY are synthesized. Firstly, BDBrC containing carbazole and BODIPY core is synthesized. Cellular uptake research shows BDBrC can target on lysosome and singlet oxygen generation research result indicates that BDBrC can be used in photodynamic therapy. BDBrC also shows pH-sensitive …

High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig

Publications and Research

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the …

The Phase Behavior Of Ubqln Proteins And Implications For Protein Quality Control, Yiran Yang

Dissertations - ALL

The ubiquitin-proteasome system (UPS) and autophagy are essential pathways for maintaining protein quality control (PQC) in cells. Misfolded proteins and large aggregates are cleared by UPS and autophagy signaled by ubiquitin (Ub) or polyubiquitin (polyUb) chains. Shuttle proteins facilitate cargo transporting by interacting with both ubiquitin and degradation machineries. Previously, our lab discovered that the shuttle protein Ubiquilin-2 (UBQLN2) is recruited to stress granules in cells and undergoes liquid-liquid phase separation (LLPS) in vitro. LLPS is a biophysical process by which proteins separate themselves from the surrounding aqueous solution by forming protein-rich droplets. The overarching goals of this work are …

Single-Variable Porous Nanomaterial Series From Polymer Structure-Directing Agents, Morgan Stefik

Faculty Publications

Block polymer structure-directing agents (SDA) enable the production of porous nanoscale materials. Most strategies rely upon polymer equilibration where diverse morphologies are realized in porous functional materials. This review details how solvent selectivity determines the polymer SDA behaviors, spanning from bulk-type to solution-type. Equilibrating behavior of either type, however, obscures nanostructure cause-and-effect since the resulting sample series convolve multiple spatial variations. Solution-type SDA behaviors include both dynamic and persistent micelles. Persistent micelle templates (PMT) use high solvent selectivity for kinetic entrapment. PMTs enable independent wall thickness control with demonstrated 2 Å precision alterations. Unimodal PMT pore size distributions have spanned …

Genetically Engineered Thermosynechococcus Elongatus Bp1: Assessment Of Potential Biorisks And Biofuel Production, Thu Ho Anh Nguyen-Jones

Chemistry & Biochemistry Theses & Dissertations

According to the International Energy Outlook 2019, released by the U.S. Energy Information Administration, it is projected that the energy consumption will increase up to 50% between 2018 and 2050 worldwide. As fossil fuel being a finite source of energy with the risk of depletion, many countries are now facing an energy security crisis. Therefore, it is important to develop other renewable and sustainable energy sources that will allow countries to shift away from depending on fossil fuels. Among several types of renewable energy, biofuel production using genetically engineered cyanobacteria is capturing much interest due to its many advantages. Different …

College Of Natural Sciences Newsletter, December 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 12

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 2 Media Coverage of CNS
Page 3 Media Coverage Cont.
Page 4 Science as Art Competition
Page 5 Open PRAIRIE Data
Page 5 Grants Awarded in CNS

Spectroscopic Studies Of The Interaction Between Phosphorus Heterocycles And Cytochrome P450, Dumei Ma, Libo Zhang, Yingwu Yin, Yuxing Gao, Qian Wang

Faculty Publications

P450 fatty acid decarboxylase OleT from Staphylococcus aureus (OleT_SA) is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO₂ or minor α- and β-hydroxylated fatty acids as side-products. In this work, the interactions between a series of cycloalkyl phosphorus heterocycles (CPHs) and OleT_SA were investigated in detail by fluorescence titration experiment, ultraviolet–visible (UV–vis) and ³¹P NMR spectroscopies. Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6, a representative CPHs, interacted with OleT_SA with a binding constant value of 15.2 …

Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale

Graduate Theses and Dissertations

Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …

3-Dimensional Structural Determination Of Epidermal Growth Factor-Like Repeat 27 From Mouse Notch1 Using Nuclear Magnetic Resonance Spectroscopy, Justin Grennell

LSU Doctoral Dissertations

NOTCH1 has been associated with a variety of human ailments, such as cancer and heart disease. NOTCH1 is a transmembrane protein that contains 36 epidermal growth factor-like (EGF) repeats, which facilitate cell signaling by binding proteins on neighboring cells. Each repeat contains about 40 amino acids and has to be folded in a specific manner to function properly. The amino acid sequence, carbohydrate pattern, and calcium-binding sites of EGF-like repeats vary, but the pattern along the 36-repeat chain is conserved. The Abruptex region (EGF24-29) of NOTCH1 is a highly glycosylated (having undergone sugar addition) and flexible region, which gained its …

Investigation Of Immobilized Enzymes In Confined Environment Of Mesoporous Host Matrices, Xiaoliang Wang

USF Tampa Graduate Theses and Dissertations

Enzyme immobilization in metal-organic frameworks (MOFs) as a promising strategy, is attracting the interest of scientists from different disciplines with the expansion of MOF’s development. Different from other traditional host materials, their unique strengths of high surface areas, large yet adjustable pore sizes, functionalizable pore walls, and diverse architectures make MOFs an ideal platform to investigate hosted enzymes, which is critical to the industrial and commercial process. In addition to the protective function of MOFs, the extensive roles of MOFs in the enzyme immobilization are being well-explored by making full use of their remarkable properties like well-defined structure, high porosity, …

College Of Natural Sciences Scholarship Brunch Program, November 6th 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

This is the program for the first annual College of Natural Sciences Scholarship Brunch, held on November 6th, 2021 at McCrory Gardens.

College Of Natural Sciences Newsletter, November 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 11

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 3 Media Coverage of CNS
Page 4 2021 Day of Scholars
Page 5 Astronomy Outreach
Page 6 SDSU Faculty & Students Host American Society for Microbiology Annual Conference
Page 7 Scholarship Brunch
Page 8 Open PRAIRIE Data, SI Final Exam Review Sessions
Page 9 Aamlid Family Anatomy Lab Photos

Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …

A Nosy Neighbor: Purification And Functional Characterization Of Lpg2149, Ashley M. Holahan

The Journal of Purdue Undergraduate Research

Ubiquitination is a process that marks proteins for various cell-signaling pathways, namely protein degradation and other processes. Th ese pathways are essential in a wide array of cellular processes, including defense mechanisms against invading pathogens. Th e ubiquitination process is universally found in all eukaryotic organisms, including plants and animals, and thus plays a vital role in cellular homeostasis. Recently, more discoveries have been made on prokaryotic effector proteins that hijack the ubiquitination system even when they do not possess a ubiquitin system of their own. MavC, also known as lpg2147 (Gan, Nakayasu, Hollenbeck, & Luo, 2019; Puvar et al., …

College Of Natural Sciences Newsletter, October 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 10

Page 1 Dean's Message
Page 2 Awards and Recognition; Introducing Natural Sciences Student Ambassadors
Page 3 Media Coverage of CNS
Page 4 Spooky Science Outreach
Page 5 The BIG Event Outreach
Page 6 Geography Club Road Trip
Page 7 Aamlid Family Anatomy Lab
Page 8 Hobo Day Recap
Page 10 Open PRAIRIE Data; Grants Awarded in CNS

Settingsorder Article Reprints Open Accessarticle Generation And Characterization Of Human Mesenchymal Stem Cell-Derived Smooth Muscle Cells, Srikanth Sivaraman, Jackson Hedrick, Samia Ismail, Chris Slavin, Raj R. Rao

Biomedical Engineering Faculty Publications and Presentations

Cardiovascular diseases are the leading cause of death worldwide. A completely autologous treatment can be achieved by using elastogenic mesenchymal stem cell (MSC)-derived smooth muscle cells (SMC) at the affected tissue site of vascular diseases such as abdominal aortic aneurysms (AAA). Thus, our work focused on evaluating the efficacy of (a) the combination of various growth factors, (b) different time periods and (c) different MSC lines to determine the treatment combination that generated SMCs that exhibited the greatest elastogenicity among the tested groups using Western blotting and flow cytometry. Additionally, total RNA sequencing was used to confirm that post-differentiation cells …