Digital Commons Network^™

Strad Pseudokinases Regulate Axogenesis And Lkb1 Stability, Biliana O. Veleva-Rotse, James L. Smart, Annette F. Baas, Benjamin Edmonds, Zi-Ming Zhao, Allyson Brown, Lillian R. Klug, Kelly Hansen, Gabrielle Rielly, Alexandria P. Gardner, Krishnaveni Subbiah, Eric A. Gaucher, Hans Clevers, Anthony P. Barnes

Faculty Publications - Department of Biological & Molecular Science

No abstract provided.

Mentoring Undergraduates Via Organic Synthesis, Steven L. Castle

Journal of Undergraduate Research

This report summarizes the results of the mentoring environment in my laboratory that were generated from January 2012 to present. During this period, a total of seven undergraduates performed research in my laboratory. Their names and accomplishments are listed below.

An Ethnobotanical, Ecological And Lc-Ms-Based Chemometric Investigation Of Phaleria Nisidai, A Traditional Adaptogen Containing Diterpene Esters From Palau, Micronesia, Daniel Kulakowski

Dissertations, Theses, and Capstone Projects

An ethnobotanical, ecological and LC-MS-based chemometric investigation of Phaleria nisidai, a traditional adaptogen containing diterpene esters from Palau, Micronesia

Palau is a country with a rich heritage of traditional medicine still being practiced. One of the most popular and respected remedies in Palau is a tea made from fresh leaves of Phaleria nisidai Kaneh. (Thymelaeaceae). Interviews conducted to determine the use of this plant revealed that it is employed non-specifically to treat a variety of general health concerns. Its use as a prophylactic to keep away sickness, as a 'system cleaner', as well as for strength and energy indicate …

The Role Of Rnase L In Thymic Homeostasis And Humoral Responses, Lin Zhang

ETD Archive

RNase L is highly expressed in the spleen, thymus, and multiple immune cells, suggesting that it may play an important role in the immune system against microbes. Previous studies in the lab have shown that deficiency of RNase L results in enlarged thymuses in mice at young age. However, relatively little is known about its influence on the thymic development and adaptive immunogenicity. The present Ph.D. study focuses on investigating the role of RNase L in the thymic homeostasis and humoral immune responses, thereby gaining new insights into the molecular aspects in thymocyte development, maturation and adaptive immunity.By using RNase …

Probing Proteasome Inhibition By Metal Copmplexes As A New Route For Anticancer Therapy, Dajena Tomco

Wayne State University Dissertations

The scope of this thesis is focused towards the development of metal-containing coordination compounds as potential therapeutic agents. Efforts of this research involve the design, synthesis, and purification of these complexes, as well as their evaluation by spectroscopic, spectrometric, and electrochemical characterization. The antineoplastic properties of these metal-containing pro-drugs are tested against the inhibition activity of the 26S proteasome. Selected metal ions ranging from transition to main group elements have been incorporated in various ligand systems containing phenolate and pyridyl donor sets. The mechanistic behavior of these complexes in solution has been thoroughly investigated along with their in vitro anticancer …

Investigation Into The Binding Interactions Of Klenow Fragment To Dna Modified With Carcinogens Af And Aaf Using Surface Plasmon Resonance, Ashley M. Floyd

Wayne State University Dissertations

The two major forms of DNA adducts from the carcinogen N-acetoxyacetyl-2-aminofluorene, N-(deoxygunanonsin-8-yl)-2-acetylaminofluorene (dG-C8-AAF) and N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), are both known to impede replication, though in different ways. AAF is a strong block to replication leading to frameshift mutations, while the AF adduct is more easily bypassed, causing base substitutions. Surface plasmon resonance (SPR) was used to study the binding of exonuclease deficient E. coli polymerase I, Klenow fragment (KF), to DNA modified with AF or AAF at two locations: as a templating base or in the last formed base pair. KF binding to the modified DNA bases was also monitored to …

Antioxidant, Anticholinesterase, And Antimicrobial Activities And Fatty Acid Constituents Of Achillea Cappadocica Hausskn. Et Bornm., Abdulselam Ertaş, Mehmet Boğa, Nesri̇n Haşi̇mi̇, Yeter Yeşi̇l, Ahmet Ceyhan Gören, Gülaçti Topçu, Ufuk Kolak

Turkish Journal of Chemistry

This study was the first fatty acid analysis and biological activity report on an endemic Achillea species, Achillea cappadocica Hausskn. et Bornm. The major compounds in the fatty acid were identified as oleic (34.7 %), palmitic (23.1 %), and linoleic acids (20.6 %). The methanol and water extracts indicated higher ABTS cation radical scavenging activity than that of \alpha-tocopherol and BHT at 100 \mu g/mL. The acetone extract showed 70.62 % inhibitory activity against butyrylcholinesterase at 200 \mu g/mL. The acetone and methanol extracts exhibited moderate antimicrobial activity.

Synthesis, Anticandidal Activity, And Cytotoxicity Of Some Thiazole Derivatives With Dithiocarbamate Side Chains, Leyla Yurttaş, Yusuf Özkay, Fati̇h Demi̇rci̇, Gamze Göger, Şafak Ulusoylar Yildirim, Usama Abu Mohsen, Ömer Öztürk, Zafer Asim Kaplancikli

Turkish Journal of Chemistry

Some thiazole derivatives bearing dithiocarbamic acid esters were synthesized in order to investigate their anticandidal activity and cytotoxicity. The structures of the obtained final compounds (6a--j) were confirmed by spectral data (IR, ^1H NMR, ^{13}C NMR, and MS) and elemental analysis. The anticandidal activity of the compounds was determined (6a--j) using the microbroth dilution method and their cytotoxicity was evaluated according to the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against normal cells. Contrary to expectations, weak antifungal activity was observed with IC_{50} values ranging between 30 and 403 \mu g/mL.

Monitoring Ligand-Induced Nucleic Acid Conformational Changes Using Ion Mobility Spectrometry-Mass Spectrometry, Bill Kenneth Redick

Legacy Theses & Dissertations (2009 - 2024)

Three-dimensional structures of biopolymers frequently dictate the biological role those molecules play. As such, investigation into structure of nucleic acids can provide important information pertaining to how those nucleic acids work. Many nucleic acid species, especially single-stranded RNA, fold into unique structures that allow them to function properly. Metals, and other cationic species, are often bound to the nucleic acid to make folding into the proper structure more favorable by neutralizing the negative charge on the nucleic acid imparted by the phosphate group. This investigation explores tertiary structure of nucleic acids that have been folded in the presence of ligands …

Genetic And Biochemical Studies Of Human Apobec3h Enzyme, Thisari Sachithra Aluthgama Guruge

Wayne State University Theses

The AID/APOBEC enzymes are DNA/RNA cytosine deaminases with important functions in innate and adaptive immunity. APOBEC3 enzymes play a crucial role in restricting the replication of exogenous retroviruses such HIV-1 and endogenous retrotransposition events. In particular, APOBEC3 enzymes have evolved in humans by gene duplication to compose seven members. APOBEC3H is highly diverse in its allelic sequence and the distribution is population-specific. It has evolved under strong positive selection over millions of years. To study the catalytic mechanism, structure, function and the underlying cause of its high diversity, a high resolution crystal or NMR structure is required are not yet …

Synthesis And Study Of Chemo-Hydrothermally Derived Water-Soluble Chitosan And Chiosan-Metal Oxide Composites, Srijita Basumallick

Electronic Theses and Dissertations

Chitosan (CS) is a man-made sugar based biopolymer derived from chitin, the second most abundant natural polymer after cellulose. Chitin is sourced from crustacean species such as shrimps and crabs. The chemical structure of chitin contains N-Acetyl D-glucosamine monomer units which forms CS upon deacetylation. In CS, ?-(1-4) linked D-glucosamine units are randomly distributed. Approximately 75% - 80% sugar units contains primary amine groups in commercially available low molecular weight CS. Biodegradability, low toxicity, mucoadhesive and transfecting properties of CS polymer are attractive for applications as oral and nasal drug delivery systems. Chitosan polymer is water insoluble at neutral pH. …

Phosphatase-Inert Glucosamine 6‑Phosphate Mimics Serve As Actuators Of The Glms Riboswitch, Xiang Fei, Thomas Holmes, Julianna Diddle, Lauren Hintz, Dan Delaney, Alex Stock, Danielle Renner, Molly Mcdevitt, David B. Berkowitz, Juliane K. Soukup

David Berkowitz Publications

The glmS riboswitch is unique among generegulating riboswitches and catalytic RNAs. This is because its own metabolite, glucosamine-6-phosphate (GlcN6P), binds to the riboswitch and catalytically participates in the RNA selfcleavage reaction, thereby providing a novel negative feedback mechanism. Given that a number of pathogens harbor the glmS riboswitch, artificial actuators of this potential RNA target are of great interest. Structural/kinetic studies point to the 2- amino and 6-phosphate ester functionalities in GlcN6P as being crucial for this actuation. As a first step toward developing artificial actuators, we have synthesized a series of nine GlcN6P analogs bearing phosphatase-inert surrogates in place …

Light Mediated Drug Delivery Using Photocaged Molecules And Photoswitchable Peptides, Deboleena Mitra

Theses and Dissertations

There are many different types of targeted therapy for cancer treatment. The method of light mediated targeted therapy that we have developed uses photocaged molecules and photoswitchable peptides.

In photocaging, a biologically active molecule is made inactive by the attachment of a photocleavable blocking group. On exposure to UV radiation the photocleavable entity is removed and the biologically active molecule is released. Using this concept we have designed a prodrug that consists of a cell impermeable hydrophilic molecule attached to a photocaged doxorubicin. Upon irradiation with UV light the photosensitive group is removed and cytotoxic doxorubicin is released at the …

Synthesis Of Resveratrol Ester Derivatives, Daniel Ressler

Electronic Theses and Dissertations

The goal of this research project was to synthesize derivatives of transresveratrol. In order for resveratrol to be activated and used by the body it needs to bind to Human Serum Albumin (HSA), a protein in blood plasma. The derivatives were synthesized to improve the ability of resveratrol to enter cells as well as improve their ability to bind to HSA. The three derivatives that were synthesized have converted one of the hydroxyl groups on resveratrol to an ether with a methylene chain terminated by a carboxylic acid. By varying the lengths of the methylene chain we varied the water …

Synthesis And Characterization Of Novel Amino-Retinoid A4-Spermine, Jeffrey Swallow, Dr. Heidi Vollmer-Snarr

Journal of Undergraduate Research

Age Related Macular Degeneration (AMD) is the leading cause of vision loss in developed countries. The accumulation of lipofuscin in the eye causes death of the retinal pigment epithelium (RPE) leading to blindness (1,2). The lipofuscin chemical A2E has been shown to have cytotoxic effect in RPE, yet much of lipofuscin has remained uncharacterized (3). We have shown that other compounds exist in lipofuscin through preliminary mass spectroscopy (MS) and high-pressure liquid chromatography (HPLC) data collected from lipofuscin samples. Our lab is working to first characterize these lipofuscin compounds and then we will also study their oxidative products in order …

Function And Distribution Of Apolipoprotein A1 In The Artery Wall Are Markedly Distinct From Those In Plasma, Joseph A. Didonato, Ying Huang, Kulwant S. Aulak, Orli Even-Or, Gary Gerstenecker, Valentin Gogonea, Yuping Wu, Paul L. Fox, W.H. Wilson Tang, Edward F. Plow, Jonathan D. Smith, Edward A. Fisher, Stanley L. Hazen

Chemistry Faculty Publications

Background—Prior studies show that apolipoprotein A1 (apoA1) recovered from human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the lipoprotein. Remarkably, no studies to date directly quantify either the function or HDL particle distribution of apoA1 recovered from the human artery wall. Methods and Results—A monoclonal antibody (10G1.5) was developed that equally recognizes lipid-free and HDL-associated apoA1 in both native and oxidized forms. Examination of homogenates of atherosclerotic plaque–laden aorta showed >100-fold enrichment of apoA1 compared with normal aorta (P<0.001). Surprisingly, buoyant density fractionation revealed that only a minority (<3% of total) of apoA1 recovered from either lesions or normal aorta resides within an HDL-like particle (1.063≤d≤1.21). In contrast, the majority (>90%) …

Development Of Novel Reaction-Based Fluorescent Probes, Weimin Xuan

Chemistry and Chemical Biology ETDs

Fluorescent probes have been proved to be very valuable tools in chemical and biological applications, and extensive exploration has been made. Recently, reaction-based fluorescent probes became a new design trend and displayed great potential with remarkable implementation to the conventional design method. However, this field is still underdeveloped, and a lot of problems remain to be solved. As part of our groups research interest, my Ph.D. study centered on the development of new reaction-based fluorescent probes. Firstly, our previous research on Hg²⁺ was continued. In this work, we developed a novel ratiometric fluorescent probe for Hg²⁺ with impressive …

Bcl-2 Promoter Sequence G-Quadruplex Interactions With Three Planar And Non-Planar Cationic Porphyrins: Tmpyp4, Tmpyp3, And Tmpyp2., Vu H. Le, Narayana Nagesh, Edwin A. Lewis

CAS Publications

The interactions of three related cationic porphyrins, TMPyP4, TMPyP3 and TMPyP2, with a WT 39-mer Bcl-2 promoter sequence G-quadruplex were studied using Circular Dichroism, ESI mass spectrometry, Isothermal Titration Calorimetry, and Fluorescence spectroscopy. The planar cationic porphyrin TMPyP4 (5, 10, 15, 20-meso-tetra (N-methyl-4-pyridyl) porphine) is shown to bind to a WT Bcl-2 G-quadruplex via two different binding modes, an end binding mode and a weaker mode attributed to intercalation. The related non-planar ligands, TMPyP3 and TMPyP2, are shown to bind to the Bcl-2 G-quadruplex by a single mode. ESI mass spectrometry experiments confirmed that the saturation stoichiometry is 4:1 for …

Studies Toward The Synthesis Of Lyconadin A And Cranomycin, Brad M. Loertscher

Theses and Dissertations

Lyconadin A is a pentacyclic Lycopodium alkaloid isolated from the club moss Lycopodium companatum with anticancer activity. Our approach sought to incorporate a 7-exo–6-exo acyl radical cyclization cascade to access the bicyclo[5.4.0]undecane framework of lyconadin A. Our studies created methodology for the synthesis of 5-alkyl and 3,5-dialkyl-6-carbomethoxy-2-pyridones and sterically demanding epoxide substrates. These epoxide substrates underwent an unanticipated Payne rearrangement.Cranomycin is a potent antibiotic with antiprotozoal activity. Structurally it is a cyclopentane ring system with substitution at each carbon in the ring. Another interesting structural aspect is the existence of three contiguous quaternary stereocenters including two tertiary alcohols and a …

Synthesis And Antifungal Evaluation Of Barbiturate Saponins And Progress Towards Cysteinyl Metal Peptides, Monika Madhav

LSU New Orleans Theses and Dissertations

Invasive fungal infections are a major threat to immune-compromised patients. There is a critical need to develop new antifungal agents because of increasing resistance to the common antifungal drugs.

In the first part of this dissertation, methods for preparation of novel barbiturate saponin as antifungals and their biological activities would be described. Barbiturates and steroidal saponins have shown remarkable antifungal activity in the biological assays. Therefore, attempts were directed to combine the barbiturate with the steroid to give novel antifungal agents. The need for extensive SAR studies and to better understand these compounds efforts were directed to synthesize novel saponin …

I. Stereochemical Control Of Chiral Assembly And Liquid Crystal Phase Formation Of Nonamphiphilic Molecules In Water Ii. Control Bacterial Quorum Sensing And Quorum Sensing-Mediated Activities Using Small Unnatural Molecules, Sijie Yang

Chemistry - Dissertations

The primary goal of this research is to utilize organic synthesis as a tool to prepare small molecules that find potential application in different areas including colloidal and material science, biological chemistry, and medicinal chemistry.

Chapter 1 describes the interpretation of the conformation of nonamphiphilic mesogen disodium cromoglycate (5´DSCG) when it exists as part of an assembly in water. The study of thermodynamic incompatibility and miscibility suggest that a previously proposed model for the assembly of 5´DSCG may be applicable to nonamphiphilic organic dyes and other mesogens.

Chapter 2 presents a study of stereochemical control on assembly and liquid crystal …

Synthesis Of Dibenzofurans Via A Palladium Catalyzed Oxidative Ring Closure Reaction, Sadia Akram

Senior Honors Theses

The cannabinoid partial agonist BAY 59-3704 has been identified as an attractive target to explore structure-activity relationships at cannabinoid receptors for the development of a therapeutic agent for psychostimulant addiction. This thesis will describe the studies associated with the optimization of a palladium-catalyzed oxidative ring closure reaction for the synthesisof dibenzofuran analogues from substituted diaryl ethers. These dibenzofurans are viewed as rigid analogues of BAY 59-3704 and will provide useful information about molecular interactions at cannabinoid receptors. The scope and limitations of the palladium-catalyzed oxidative ring closure reaction as it relates to the synthesis of the target dibenzofuran analogues will …

Interaction Of Ruthenium Polypyridyl Complexes With Human Telometric Dna, Vienna Tran , '13

Senior Theses, Projects, and Awards

The goal of this thesis work was to explore the interactions between a series of ruthenium complexes and the human telometric DNA sequence. Specifically, this work investigated the ability of [Ru(bpy)₂L]²⁺ and [Ru(phen)₂L]²⁺ complexes to act as G-quadruplex (GQ) stabilizing ligands (bpy = bipyridine, phen = phenanthroline, L = a polypyridyl derivative of dipyridophenazine (dppz)). [Ru(bpy)₂(dppz)]²⁺ and [Ru(phen)₂(dppz)]²⁺ are known to bind to GQ DNA, though not selectively and also to display molecular light switch activity upon interaction with DNA. The ruthenium complexes were studied in this work with several UV-visible and fluorescent techniques to determine the ability of each …

Expulsion Of Leaving Groups From Zwitterionic Intermediates Generated Via Photochemical Electrocyclic Ring Closure Reactions And An Investigation On Tpe Oligomers, Tasnuva Shahrin

Dissertations (1934 -)

Photochemical cleavage reactions have been found widespread use in biological applications that require intracellular photochemical release of biologically active substrates such as peptides, proteins, neurotransmitters, or nucleotide phosphates. The research is to devise photoremovable protecting groups (cage compounds) that can be used to deprotect those biological substrates by irradiation. A number of photocleavage reactions have been developed in recent years which release chlorides, hydroxides, carboxylates, thiolates, and phenolates leaving groups for use in such applications. Nevertheless, photochemical elimination reactions that expel such leaving group anions remain quite uncommon. The cleavage of cage compounds via photolysis requires heterolysis of a bond …

Analysis Of Beetle Cuticular Hydrocarbons, Elizabeth A. Williams , '13

Senior Theses, Projects, and Awards

The insect cuticle, commonly known as the exoskeleton, consists of two layers: a bottom layer called the procuticule and a thin outer waxy coating called the epicuticle. The epicuticle contains hydrocarbons that prevent desiccation and are used for chemical communication both inter- and intra- specifically. For some insects, these compounds are important sociochemicals involved in recognizing nestmates and predators as well as identifying the sex of other insects. The established procedure to extract cuticular hydrocarbons is lethal, directly introducing the insects to toxic solvents. The goal of this study is to develop a non-lethal procedure to extract the cuticular hydrocarbons …

Molecular Docking And Qsar Study On Imidazole Derivatives As 14 /Alpha -Demethylase Inhibitors, Asghar Davood, Maryam Iman

Turkish Journal of Chemistry

14\alpha-Demethylase (CYP51) inhibitors have been widely used in the treatment of fungal infections. In this study, a series of imidazole derivatives with CYP51 inhibitory activity were subjected to a molecular docking study followed by quantitative structure-activity relationship (QSAR) analyses in search of the ideal physicochemical characteristics of potential CYP51 inhibitors. Desired imidazoles were built using the HyperChem program, and conformational studies were performed through a semiempirical method followed by the PM3 method. Docking study was performed using the AutoDock program on all of the compounds. Different QSAR descriptors were calculated using DRAGON, AutoDock, and HyperChem. Multilinear regression was used as …

(S)-Trifluoroselenomethionine : A New Non-Natural Amino Acid With Enhanced Methioninase-Induced Cytotoxicity Toward Human Colon Cancer Cells, Stephene Nathele Lodge

Legacy Theses & Dissertations (2009 - 2024)

Abstract

Synthetic Efforts Toward The Eastern Hemisphere Of Theonellamide C, Douglas D. Wong

LSU Doctoral Dissertations

The theonellamides (TNMs) A-F are bicyclic dodecapeptides isolated from marine sponges of the genus Theonella and were shown to display potent antifungal activity. Despite considerable synthetic effort to produce TNM F by the Shioiri group in the early 1990s, a total synthesis of a TNM has yet to be reported. This dissertation describes our efforts toward some of the required amino acid residues of TNM C and the eastern hemisphere. The production of erythro-β-hydroxyasparagine (eHyAsn) followed the synthesis of threo-β-HyAsn by Boger and co-workers, utilizing a key Sharpless aminohydroxylation reaction. The eHyAsn building block, Boc-eHyAsn(OTBS)-OH, was coupled with HCl.Phe.OMe using …

Synthesis, Characterization And Biological Studies Of Carboranyl-Porphyrin Bioconjugates For Treatment Of Brain Tumors, Naga Venkata Satya Dinesh Kumar Bhupathiraju

LSU Doctoral Dissertations

Chapter 1 gives a brief introduction to brain tumors, approaches to deliver drug across the blood brain barrier (BBB), boron neutron capture therapy (BNCT) for brain tumors, application of carboranyl derivatives in attempt to treat brain tumors using BNCT. Chapter 2 involves synthesis, characterization and toxicity studies (In vitro and In vivo) of high boron containing pegylated cobaltabisdicarbollide porphyrin for treatment of brain tumors using BNCT. To improve the selectivity towards brain tumors we attempted conjugate several peptides to this non-toxic pegylated cobaltabiscabollide porphyrin. In vivo studies were conducted in collaboration with Dr. David G. Baker at LSU veterinary Medicine. …

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …