Chemistry Commons^™

A Case In Kinase 2 Inhibitor Is A Potent Anti-Cancer Drug Candidate, Alieta Ciocea

ETD Archive

Cancer is so widespread and lethal that it can be considered the biggest health problem of our century. Cancer drug development is a real challenge. Efforts outlined in this work were directed towards showing solid evidence that casein kinase 2 inhibitors can be used as a starting point for the development of potential cancer therapy. We first studied the effect of a specific CK2 inhibitor, DMAT, in a malignant megakaryoblastic leukemia cell line (MEG-01). Treated cells grew at a significantly lower rate than non-treated cells. Apoptosis was induced by DMAT in MEG-01 cells, dose and time dependent. When stimulated with …

Development Of Oligonucleotide Microarray For High Throughput Dna Methylation Analysis, Xiaopeng Li

ETD Archive

DNA methylation is a key event regulating gene expression. DNA methylation analysis plays a pivotal role in unlocking association of epigenetic events with cancer. However, simultaneous evaluation of the methylation status of multiple genes is still a technical challenge. Microarray is a promising approach for high-throughput analysis of the methylation status at numerous CpG sites within multiple genes of interest. In this dissertation study, we conducted a systematic study to examine the use of microarray methods for methylation analysis. First, a robust universal microarray was established with more flexible in design and content, and potential cost saving over commercial arrays. …

Technologies For Proteomic And Genomic Biomarker Analysis, Yiding Liu

ETD Archive

In the first part of this dissertation, we systematically validated the application of molecular weight cut-off ultrafiltration in separation and enrichment of low-molecular-weight peptides from human serum. Under optimized conditions, both free-phase and bound LMW peptides could be separated and enriched. The method proved to be highly efficient and reproducible coupled with MALDI-TOF MS proteomic pattern analysis. Three marker peaks were found to be eligible for distinguishing normal and ovarian cancer samples. A novel organic solvent precipitation method coupled with enzymatic deglycosylation was also developed for biomarker detection from human serum. This method allowed us to generate reproducible free-phase peptide …

Inhibition Of The Nf-Kb Signaling Pathway And Its Effects On Apoptosis And Cancer, Joseph A. Lupica

ETD Archive

The Rel/NF-kB family of inducible transcription factors are evolutionarily conserved structurally and functionally, from insects to humans. They are ubiquitously expressed in a number of mature cell types, playing a pivotal role regulating cell growth, differentiation and apoptosis. Under normal circumstances, the proliferation of new cells is tightly regulated, as is the programmed lifespan of most cells, occasionally however cells loose their responsiveness to growth control mechanisms, resulting in a tumor or neoplasm. Sustained or chronic inflammation has been linked to a number of pathological conditions that destroy tissue and facilitate neoplastic growth. NF-kB in part mediates the opposing signals …

High Temperature Volatility And Oxidation Measurements Of Titanium And Silicon Containing Ceramic Materials, Quynhgiao N. Nguyen

ETD Archive

Titanium (Ti) and silicon (Si) containing materials are of high interest to the aerospace industry due to its high temperature catability, strength, and ligh weight. A continuous exterior oxide layer is desirable to reduce the oxidation rate of these two materials. At high temperatures, water vapor plays a key role in the volatility of materials including oxide surfaces. This study first evaluated several hot-pressed Ti and Si-containing compositions at high temperatures as a function of oxidation environments to determine the volatile hydoxy! species using the transpiration method. The water content ranged from 0-76 mole and the oxygen content range was …

Modeling The Human Prothrombinase Complex Components, Tivadar Orban

ETD Archive

Thrombin generation is the culminating stage of the blood coagulation process. Thrombin is obtained from prothrombin (the substrate) in a reaction catalyzed by the prothrombinase complex (the enzyme). The prothrombinase complex is composed of factor Xa (the enzyme), factor Va (the cofactor) associated in the presence of calcium ions on a negatively charged cell membrane. Factor Xa, alone, can activate prothrombin to thrombin however, the rate of conversion is not physiologically relevant for survival. Incorporation of factor Va into prothrombinase accelerates the rate of prothrombinase activity by 300,000-fold, and provides the physiological pathway of thrombin generation. The long-term goal of …

Synthesis And Characterization Of Acylphosphine Oxide Photoinitiators, Hany F. Sobhi

ETD Archive

Recently, polymerization science has assumed an increasing relevance in many applications, including orthopedic and dental biomaterials. Current technologies are based on the use of photochemically reactive systems, which are suited to absorb light to produce primary radical species capable of initiating polymerization. Acylphosphine oxides and acylphosphonates are known to be very effective photoinitiators for various unsaturated polymeric systems. The high reactivity observed was ascribed to the phosphinyl and phosphinoyl radicals generated. Because of the poor qualities of other initiators, we examined new routes to synthesize acylphosphine oxide initiators to achieve compatibility with aqueous media and improved performance. The preparation and …

Mass Spectrometry-Based High Throughput Approach For Identification Of Molecular Modification Of Oxidative Process In Respiratory Diseases, Wei Song

ETD Archive

Eosinophil peroxidase (EPO) and myeloperoxidase (MPO) have been implicated in generating reactive species and promoting oxidative modifications in numerous diseases. The detection and identification of potential pathways has been proven extremely challenge due to evanescence nature of these reactive species. An alternative approach to study the involvement of oxidative modification is to detect and quantify the stable molecular fingerprints, like oxidized tyrosine species, in biological matrices. Previously reported analytical methods for quantifying oxidized amino acids have typically been limited by: low sensitivity, specificity and the failure of detection potential oxidation products generated during sample handling. Using GC/MS in combination with …

Study Of 3'-Untranslated Region Of Inducible Nitric Oxide Synthase And Identification Of Other Targets Of Gaitpathway, Sirisha Vadlamani

ETD Archive

Macrophages and other leukocytes play a vital role during inflammation. IFN-Îđ which is secreted by Th1 cells activates monocyte-macrophages and this activation leads to induction as well as suppression of certain genes expressed during inflammation. This suppression of genes may be potentially vital for resolution of inflammation. Upon IFN-Îđ stimulation, a Gamma-activated inhibitor of translation complex (GAIT) is formed, which binds to 3'-UTR of target mRNAs thereby silencing their translation. VEGF-A and ceruloplasmin are two proteins whose translation is suppressed by this pathway. The GAIT complex proteins have been identified as ribosomal protein L13a, glutamyl-prolyl tRNA synthatase (EPRS), NS-1 associated …

Interactions Of Cis-Bis Ruthenium Complexes With Monosaccharides, Lindsay Mcdonald

Undergraduate Review

Molecular recognition and binding of oligosaccharides play an essential role in many biological processes including cell-cell recognition, signaling and adhesion. Our group is currently involved in the development of metal based receptors that can effectively bind specific glycoconjugates. Species that can selectively bind and chemically alter membrane glycoconjugates have the potential to inhibit tumor cell metastasis, inflammation and fibrosis. As an initial step towards our goal the interactions of cis-Ru(bpy)₂(DMF)₂²⁺ (bpy = bipyridine, DMF = dimethylformamide) and cis-Ru(acac)₂(CH₃CN)₂⁺ (acac = acetylacetonate) with the monosaccharides glucose and mannose have been examined …

Synthesizing And Characterizing Sr2Femoo6 Bulk And Thin Films, Louis Bianchini

Undergraduate Review

A Sr₂FeMoO₆ (SFMO) pellet was synthesized to use as a target in the Pulsed Laser Deposition (PLD) chamber. The method chosen was a solid state reaction of SrCO₃, Fe₂O₃ and MoO₃. All three materials were combined stoichiometrically, ground in a ball mixer, and annealed for 36 hours at 1000°C. A pellet press was custom designed and used to press the annealed powders into a pellet. The magnetic and structural properties of the powder were studied using a Quantum Design MPMS SQUID magnetometer and powder X-Ray diffractometer, respectively. Previous studies of …

Phosphorylation Of Claudin-5 And Occludin By Rho Kinase In Brain Endothelial Cells, Masaru Yamamoto, Servio H. Ramirez, Shinji Sato, Tomomi Kiyota, Ronald Cerny, Kozo Kaibuchi, Yuri Persidsky, Tsuneya Ikezu

Ronald Cerny Publications

Critical to the proper maintenance of blood-brainbarrier (BBB) integrity are the endothelial tight junctions (TJs). Posttranslational modifications of essential endothelial TJ proteins, occludin and claudin-5, contribute and possibly disrupt BBB integrity. Our previous work has shown that Rho kinase (RhoK) activation mediates occludin and claudin-5 phosphorylation resulting in diminished barrier tightness and enhanced monocyte migration across BBB in the setting of human immunodeficiency virus-1 encephalitis (HIVE). To determine whether RhoK can directly phosphorylate TJ proteins, we examined phosphorylation of cytoplasmic domains of recombinant claudin- 5 and occludin by RhoK. We found that RhoK predominately phosphorylated two sites on occludin (T382 …

Pennies And Eggs: Initiation Into Inquiry Learning For Pre-Service Elementary Education Teachers, D.J. Wink, J. Hwang Choe

Faculty Publications & Research

Two labs incorporating the Science Writing Heuristic are described that introduce scientific inquiry in a course for preservice students majoring in elementary education. One lab adapts a previously described discovery learning opportunity involving the change in composition and mass of pennies in 1982. The other involves the use of flotation methods to separate hard-boiled and uncooked eggs based on density. Evidence for student engagement with the method is presented, along with analysis of persistent problems with the concept of density revealed by students’ writing about their understandings.

Mass Spectrometry Of Dendrimer Metal Complexes, Jason David Batchelor

Theses, Dissertations and Capstones

Dendrimers are hyper-branched macromolecules with unique properties. They form using a “cascade-like” synthesis involving repetitive reaction steps. These steps are controlled, resulting in monodisperse dendrimers. Synthesis is divergent, core to exterior, or convergent, exterior to core. Dendrimers are created from various molecules with numerous functional properties. They are used as catalysts, diagnostic agents, and others.

This thesis studies 1st generation poly(propylene) imine, consisting of a diaminobutane core with 4 propyl amine branches. Fragmentation of protonated and metal (Co, Ni, Cu and Zn) complexed dendrimers was analyzed by ion-trap mass spectrometry. Two isotopically labeled dendrimers were synthesized for neutral loss identification …

Synthesis Towards Novel 1,3-Azaborine Heterocycles As Potential Dual-Mode Hiv-1 Protease Inhibitors, Amanda Blackmore

Undergraduate Honors Theses

Drug discovery has resulted in many life-saving therapies, making a great impact on modem medicine and the human condition. Even though new therapies are available many drugs are highly susceptible to resistance development, have poor bioavailability, and some of them are toxic. HIV-I protease inhibitors presently on the market show high specificity but have low bioavailability and high toxicity. Furthermore, the available drugs have a very low affinity for mutant forms of HIV -1 protease. Recent studies have shown that boronated HIV-I protease inhibitors, which demonstrate both competitive and associative inhibition, have a higher affinity for HIV-I protease at lower …

Synthesis And Optical Characterization Of Sry₂0₄:Eu3+, Ryan Elliot Atkins

Undergraduate Honors Theses

This paper reports on the synthesis and VUV optical characterization ofSrY2O4 doped with Eu³+. SrY2O₄:Eu³+ was synthesized from Y2O₃, Eu2O₃, and SrCO₃, with 5% excess SrCO₃ by weight; the mixture was fired at 1050 °C for 12 hrs in air twice; phase pure product was confirmed with powder X-ray diffraction. Reflectance data on an undoped sample reveals a band gap of about 6.leV. Results indicate that Eu³ occupies two non-equivalent Y sites within theSrY2O₄ framework. Calculation of maximum transfer efficiency forSrY2O₄:Eu³+ resulted in 60% with 35% lost to non-radiative decay via surface states.

Synthesis Of 5,6 Dihydropyran-2-Ones As Potential Inhibitors Of Hiv-1 Protease, Jesse Lee Nye

Undergraduate Honors Theses

HIV/ AIDS has affected about 40 million people. One type of drug that is used to treat HIV/AIDS is a protease inhibitor. HIV-I protease is an enzyme responsible for the release of mature HIV viral particles in the body. HIV-I protease eventually becomes resistant to the inhibitors that are used as drugs and new inhibitors are needed. This research builds on a previous research effort, in which structures for HIV -1 protease inhibitors were designed using molecular modeling methods, including neural networks. These inhibitors were designed to possess better inhibitory properties, and possibly have increased bioavailability and less toxicity than …

Determination Of Host To Activator Transfer Efficiences In (Y,Gd)Bo3:Eu3+ And Ybo3:Eu3+, Katie Warren

Undergraduate Honors Theses

(Y,Gd)B0₃:Eu³+ is the red phosphor in plasma displays and mercury free lamps. In this work the non-radiative host to activator energy transfer efficiency of YB0₃ :Eu³⁺ is being compared to that of (Y,Gd)B0₃ :Eu³+. Energy transfer efficiency is determined by taking excitation and reflectance spectra under vacuum ultraviolet (VUV) excitation. It is well known that co-doping YB0₃: Eu³+ with gadolinium increases the emission intensity. This research has determined that the addition of gadolinium increases the transfer efficiency.

A Streamlined Molecular Biology Module For Undergraduate Biochemistry Labs, Gregory W. Muth, Joseph W. Chihade

Chemistry Faculty Work

Site-directed mutagenesis and other molecular biology techniques, including plasmid manipulation and restriction analysis, are commonly used tools in the biochemistry research laboratory. In redesigning our biochemistry lab curricula, we sought to integrate these techniques into a term-long, project-based course. In the module presented here, students use structural data to design a site-directed mutant and make the mutation using the Ku¨ nkel method. A second, silent mutant, that creates or removes a restriction site, is simultaneously introduced. Restriction digestion and agarose gel electrophoresis are used to assess the success of mutagenesis. Placing these procedures in the context of continuous, studentdriven project …

Open Circuit Potential Shifts Of Activated Carbon In Aqueous Solutions During Chemical And Adsorption Interactions, Mikhail M. Goldin, Vladimir A. Kolesnikov, Mogely Sh. Khubutiya, Alexander G. Volkov, Gary J. Blanchard, Anatoly K. Evseev, Mark M. Goldin

Faculty Publications and Presentations

Interaction of certain inorganic and organic compounds with activated carbon and the effect of such interaction on open circuit potential of activated carbon were studied. Open circuit potential shifts were observed for an overwhelming majority of the substances and brands of activated carbons investigated. Both negative and positive potential shifts were observed. It was shown that open circuit potential shifts for organic substances depend on degree of coverage of the activated carbon surface. Whereas adsorption of investigated organic compound on activated carbon led to positive potential shifts, desorption of adsorbates from the activated carbon surface led to potential shifts in …

Synthesis, X-Ray Structure, And Bioassay Of Newly Synthesized Trimethyltin(Iv) 2,3-Methylenedioxy Benzoate, Mukhtiar Hussain, Muhammad Hanif, Saqib Ali, Saira Shahzadi, Helen S. Evans

Turkish Journal of Chemistry

Trimethyltin(IV) complex containing the carboxylate ligand 2,3-methylenedioxybenzoic acid (HL) have been synthesized and characterized in solution state by multinuclear NMR (^1H, ^{13}C and ^{119}Sn) using the noncoordinating solvent and also in solid sate by FTIR, mass spectrometry, and X-ray crystallography. Spectroscopic data have shown that methylenedioxy moiety has not coordinated with tin atom; instead, the coordination site is a -COO group, which is proved by spectral and XRD data. The solid state structure shows the trigonal bipyramidal geometry with a space group P2_1/c. This compound was tested for its in vitro antitumor activity.

New Polyamides Based On Bis(P-Amidobenzoic Acid)-P-Phenylene Diacrylic Acid And Hydantoin Derivatives: Synthesis And Characterization, Khalil Faghihi

Turkish Journal of Chemistry

Bis(p-amidobenzoic acid)-p-phenylene diacrylic acid (6) as a new monomer containing p-phenylenediacryloyl moiety was synthesized by using a 3-step reaction. At first p-phenylenediacrylic acid (3) was prepared by reaction of terephthal aldehyde (1) with malonic acid (2) in the presence of pyridine, and then diacid 3 was converted to p-phenylenediacryloyl chloride (4) by reaction with thionyl chloride. Finally bis(p-amidobenzoic acid)-p-phenylene diacrylic acid (6) was prepared by the condensation reaction of phenylenediacryloyl chloride (4) with p-aminobenzoic acid (5). Then 6 new polyamides (8a-f) containing p-phenylenediacryloyl and hydantoin moiety in the main chain were prepared by the direct polycondensation reaction of bis(p-amidobenzoic acid)-p-phenylene …

Hydrogels Of Versatile Size And Architecture For Effective Environmental Applications, Nurettin Sahiner

Turkish Journal of Chemistry

Cationic hydrogels from a positively charged monomer, (3-Acrylamidopropyl)-trimethylammonium chloride (APTMACl), were synthesized as bulk, and micro- and nano-sizes. These hydrogels were utilized to remove contaminants such as food dyes and an environmentally toxic metal, arsenic. The micro- and nanohydrogels were dispersed in another hydrogel network to design a semi-interpenetrating network (semi-IPN) which was shown to visualize the particles that can be used for absorption purposes. The micron-sized cationic hydrogel particles were very effective in the removal of arsenic from an aqueous environment- 96% of the arsenic was removed in less than 10 min from a 55-ppm aqueous stock solution. Cationic …

Cyanoacetamide Derivatives As Synthons In Heterocyclic Synthesis, Ahmed Ali Fadda, Samir Bondock, Ramy Rabie, Hassan Ali Etman

Turkish Journal of Chemistry

This review presents a systematic and comprehensive survey of the methods of preparation and the chemical reactivity of cyanoacetamide derivatives. These compounds are important intermediates for the synthesis of a variety of otherwise difficult to obtain synthetically useful and novel heterocyclic systems.

New Flame-Retardant Poly(Ester-Imide)S Containing Phosphine Oxide Moieties In The Main Chain: Synthesis And Properties, Khalil Faghihi

Turkish Journal of Chemistry

Six new flame-retardant poly(ester-imide)s (9a-f) with high inherent viscosity and containing phosphine oxide moieties in the main chain were synthesized from the polycondensation reaction of N,N-(3,3-diphenylphenyl phosphine oxide) bistrimellitimide diacid chloride (7) with 6 aromatic diols (8a-f) by 2 different methods:--solution and microwave-assisted polycondensation. The results showed that compared to solution polycondensation, the microwave-assisted polycondensation reaction using a domestic microwave oven proceeded rapidly and was completed within about 9-12 min. All of the obtained polymers were fully characterized by means of elemental analysis, viscosity measurement, solubility testing, and FT-IR spectroscopy. Thermal properties and flame retardant behavior of the PEIs (9a-f) …

Electrolytic Deposition Of Coatings For Prosthetic Metals And Alloys 2008, Jody G. Redepenning

Jody Redepenning Publications

An article coated with an electrolytically deposited biocompatible composite layer useful as an internal prosthetic device is disclosed. The bio-compatible composite coating that is electrolytically deposited onto the article comprises hydroxyapatite and chitosan. The introduction of chitosan into the crystal matrix of brushite/hydroxyapatite significantly improves the adhesive and chemical and mechanical stability properties of the coating.

Tata-Binding Protein Recognition And Bending Of A Consensus Promoter Are Protein Species Dependent, Jodell E. Whittington, Roberto F. Delgadillo, Torrissa J. Attebury, Laura K. Parkhurst, Margaret A. Daugherty, Lawrence J. Parkhurst

Lawrence Parkhurst Publications

The structure and behavior of full-length human TBP binding the adenovirus major late promoter (AdMLP) have been characterized using biophysical methods. The human protein induces a 97° bend in DNA_AdMLP. The high-resolution functional data provide a quantitative energetic and kinetic description of the partial reaction sequence as native human TBP binds rapidly to a consensus promoter with high affinity. The reaction proceeds with successive formation of three bound species, all having strongly bent DNA, with the concurrence of binding and bending demonstrated by both fluorescence and anisotropy stopped flow. These results establish the protein species dependence of the …

A General And Rapid Cell-Free Approach For The Interrogation Of Protein–Protein, Protein–Dna, And Protein–Rna Interactions And Their Antagonists Utilizing Split-Protein Reporters, Jason R. Porter, Cliff I. Stains, Benjamin W. Jester, Indraneel Ghosh

Cliff Stains Publications

Split-protein reporters have emerged as a powerful methodology for imaging biomolecular interactions which are of much interest as targets for chemical intervention. Herein we describe a systematic evaluation of split-proteins, specifically the green fluorescent protein, β-lactamase, and several luciferases, for their ability to function as reporters in completely cell-free systems to allow for the extremely rapid and sensitive determination of a wide range of biomolecular interactions without the requirement for laborious transfection, cell culture, or protein purification (12–48 h). We demonstrate that the cell-free split-luciferase system in particular is amenable for directly interrogating protein–protein, protein–DNA, and protein–RNA interactions in homogeneous …

Conserved Sequences Of Sperm-Activating Peptide And Its Receptor Throughout Evolution, Despite Speciation In The Sea Star Asterias Amurensis And Closely Related Species, Mia Nakachi, Motonori Hoshi, Midori Matsumoto, Hideaki Moriyama

Hideaki Moriyama Publications

The asteroidal sperm-activating peptides (asterosaps) from the egg jelly bind to their sperm receptor, a membrane-bound guanylate cyclase, on the tail to activate sperm in sea stars. Asterosaps are produced as single peptides and then cleaved into shorter peptides. Sperm activation is followed by the acrosome reaction, which is subfamily specific. In order to investigate the molecular details of the asterosap-receptor interaction, corresponding cDNAs have been cloned, sequenced and analysed from the Asteriinae subfamily including Asterias amurensis, A. rubens, A. jorbesi and Aphelasterias japonica, as well as Distolasterias nipon from the Coscinasteriinae subfamily. Averages of 29% and 86% identity …

Brainstem Raphe Pallidus And The Adjacent Area Contain A Novel Action Site In The Melanocortin Circuitry Regulating Energy Balance, Liugen Lei, Yan Gu, Jonathan G. Murphy, Pinxuan Yu, James L. Smart, Malcolm J. Low, Wei Fan

Faculty Publications - Department of Biological & Molecular Science

The central melanocortin system plays a critical role in the regulation of energy balance in rodents and humans. The melanocortin signals in both the hypothalamus and brainstem contribute to this regulation. However, how the melanocortin signals of the hypothalamus interact with those intrinsic to the brainstem in the regulation of energy balance is poorly understood. The brainstem raphe pallidus (RPa) and adjacent areas contain melanocortin 4 receptor (MC4-R)-bearing neurons and sympathetic premotor neurons regulating thermogenesis. Here we report that α-melanocyte-stimulating hormone (α-MSH)-immunoreactive (IR) fibers are in close apposition to MC4-R neurons in the RPa. Retrograde tracing studies revealed a unique …