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2011

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Articles 1 - 30 of 46

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

The Tetrafluoroborate Salt Of 4-Methoxybenzyl N-2-(Dimethylamino)Ethyl-N-Nitrosocarbamate: Synthesis, Crystal Structure And Dft Calculations, Helene Hedian, Vladimir Benin Dec 2011

The Tetrafluoroborate Salt Of 4-Methoxybenzyl N-2-(Dimethylamino)Ethyl-N-Nitrosocarbamate: Synthesis, Crystal Structure And Dft Calculations, Helene Hedian, Vladimir Benin

Chemistry Faculty Publications

The tetrafluoroborate salt of 4-methoxybenzyl N-2-(dimethylamino)ethyl-N-nitrosocarbamate was prepared in two steps, via the corresponding carbamate. Its crystal structure is monoclinic, space group P21/c. The unit cell dimensions are: a = 19.499(8) Å, b = 5.877(3) Å, c = 15.757(7) Å, α = 90°, β = 110.019(7)°, γ = 90°, V = 1696.5(12) Å3, Z = 4. The structure exhibits an unexpected, pseudo-gauche conformation with respect to the C2–C3 bond, due to a stabilizing hydrogen bond between the carbonyl oxygen (O1) and the hydrogen atom at the trialkylammonium center (H3n ...


Activity Of Analogs Of Anticancer Drugs On The Serine Protease Enzymes Subtilisin And Chymotrypsin, Dhatri Ravipati Dec 2011

Activity Of Analogs Of Anticancer Drugs On The Serine Protease Enzymes Subtilisin And Chymotrypsin, Dhatri Ravipati

Masters Theses & Specialist Projects

The anticancer activity of several platinum compounds is due to the formation of complexes with DNA. We hypothesize that the size and shape of the platinum compounds would impact interaction with proteins, and these interactions may be partly responsible for the anticancer activity. Chymotrypsin and subtilisin are serine proteases that have a histidine residue in the active site. We are investigating the inhibition of the digestive enzymes chymotrypsin and subtilisin by analogs of the anticancer drug cisplatin and trying to discern trends in the inhibition as the active site residues vary. In our research, we found that the enzyme subtilisin ...


Inhibition Of Cysteine Protease By Platinum (Ii) Diamine Complexes, Chaitanya Rapolu Dec 2011

Inhibition Of Cysteine Protease By Platinum (Ii) Diamine Complexes, Chaitanya Rapolu

Masters Theses & Specialist Projects

Chemotherapy is the first line of treatment used in cancer. Chemotherapy drugs such as cisplatin, carboplatin and oxaliplatin are used in treatment. Cisplatin enters the cell through copper transporter CTR1 by passive diffusion and bind to DNA and proteins. Cisplatin is found to inhibit several enzymes targeting cysteine, histidine and methionine residues, which are expected to be responsible for its anticancer activity. A better understanding of how the size and shape and leaving ligands of platinum complexes affect cysteine protease, papain enzyme are studied. This could give new ways to optimize anticancer activity. The activity of papain enzyme was measured ...


Promise Of Advances In Simulation Methods For Protein Crystallography: Implicit Solvent Models, Time-Averaging Refinement, And Quantum Mechanical Modeling, Celia Schiffer, Jan Hermans Nov 2011

Promise Of Advances In Simulation Methods For Protein Crystallography: Implicit Solvent Models, Time-Averaging Refinement, And Quantum Mechanical Modeling, Celia Schiffer, Jan Hermans

Celia A. Schiffer

No abstract provided.


Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin Nov 2011

Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational ...


Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer Nov 2011

Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

HIV-1 Vif, an accessory protein in the viral genome, performs an important role in viral pathogenesis by facilitating the degradation of APOBEC3G, an endogenous cellular inhibitor of HIV-1 replication. In this study, intrinsically disordered regions are predicted in HIV-1 Vif using sequence-based algorithms. Intrinsic disorder may explain why traditional structure determination of HIV-1 Vif has been elusive, making structure-based drug design impossible. To characterize HIV-1 Vif's structural topology and to map the domains involved in oligomerization we used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an ...


Viral Protease Inhibitors, Jeffrey Anderson, Celia Schiffer, Sook-Kyung Lee, Ronald Swanstrom Nov 2011

Viral Protease Inhibitors, Jeffrey Anderson, Celia Schiffer, Sook-Kyung Lee, Ronald Swanstrom

Celia A. Schiffer

This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HIV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is limited to viruses that cause chronic disease, viruses ...


Mutation Patterns And Structural Correlates In Human Immunodeficiency Virus Type 1 Protease Following Different Protease Inhibitor Treatments, Thomas Wu, Celia Schiffer, Matthew Gonzales, Jonathan Taylor, Rami Kantor, Sunwen Chou, Dennis Israelski, Andrew Zolopa, W. Jeffrey Fessel, Robert Shafer Nov 2011

Mutation Patterns And Structural Correlates In Human Immunodeficiency Virus Type 1 Protease Following Different Protease Inhibitor Treatments, Thomas Wu, Celia Schiffer, Matthew Gonzales, Jonathan Taylor, Rami Kantor, Sunwen Chou, Dennis Israelski, Andrew Zolopa, W. Jeffrey Fessel, Robert Shafer

Celia A. Schiffer

Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or in succession, mutation patterns of protease isolates from these persons have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 isolates from 1,919 persons with different protease inhibitor experiences: 1,004 isolates from untreated persons, 637 isolates from persons who received one protease inhibitor, and 603 isolates from persons receiving two or more protease inhibitors. The median number of protease mutations per isolate increased from 4 in untreated persons to 12 in persons who had received four ...


Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer Nov 2011

Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer

Celia A. Schiffer

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Acquired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzyme, yet determining how these flaps move at an atomic level has not been experimentally possible.

RESULTS: In the present study, we observe the flaps of HIV-1 protease completely opening during a 10 ns solvated molecular dynamics simulation starting from ...


Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren Nov 2011

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in ...


Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer Nov 2011

Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer

Celia A. Schiffer

The current effectiveness of HAART in the management of HIV infection is compromised by the emergence of extensively cross-resistant strains of HIV-1, requiring a significant need for new therapeutic agents. Due to its crucial role in viral maturation and therefore HIV-1 replication and infectivity, the HIV-1 protease continues to be a major development target for antiretroviral therapy. However, new protease inhibitors must have higher thresholds to the development of resistance and cross-resistance. Research has demonstrated that the binding characteristics between a protease inhibitor and the active site of the HIV-1 protease are key factors in the development of resistance. More ...


Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer Nov 2011

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.


Investigation Of Protein Unfolding And Stability By Computer Simulation, Wilfred Van Gunsteren, P. Hunenberger, H. Kovacs, A. Mark, Celia Schiffer Nov 2011

Investigation Of Protein Unfolding And Stability By Computer Simulation, Wilfred Van Gunsteren, P. Hunenberger, H. Kovacs, A. Mark, Celia Schiffer

Celia A. Schiffer

Structural, dynamic and energetic properties of proteins in solution can be studied in atomic detail by molecular dynamics computer simulation. Protein unfolding can be caused by a variety of driving forces induced in different ways: increased temperature or pressure, change of solvent composition, or protein amino acid mutation. The stability and unfolding of four different proteins (bovine pancreatic trypsin inhibitor, hen egg white lysozyme, the surfactant protein C and the DNA-binding domain of the 434 repressor) have been studied by applying the afore-mentioned driving forces and also to some artificial forces. The results give a picture of protein (in)stability ...


Analysis Of Binding Site Hot Spots On The Surface Of Ras Gtpase, Greg Buhrman, Casey O'Connor, Brandon Zerbe, Bradley M. Kearney, Raeanne Napoleon, Elizaveta A. Kovrigina, Sandor Vajda, Dima Kozakov, Evgueni Kovriguine, Carla Mattos Nov 2011

Analysis Of Binding Site Hot Spots On The Surface Of Ras Gtpase, Greg Buhrman, Casey O'Connor, Brandon Zerbe, Bradley M. Kearney, Raeanne Napoleon, Elizaveta A. Kovrigina, Sandor Vajda, Dima Kozakov, Evgueni Kovriguine, Carla Mattos

Chemistry Faculty Research and Publications

We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the “off” and “on” allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond ...


Re-Engineering Drug Discovery And Development, Garret A. Fitzgerald Oct 2011

Re-Engineering Drug Discovery And Development, Garret A. Fitzgerald

Issue Briefs

The rate of new drug approvals in the US has remained essentially constant since 1950, while the costs of drug development have soared. Many commentators question the sustainability of the current model of drug development, in which large pharmaceutical companies incur markedly escalating costs to deliver the same number of products to market. This Issue Brief summarizes the problem, describes ongoing governmental efforts to influence the process, and suggests changes in regulatory science and translational medicine that may promote more successful development of safe and effective therapeutics.


Development Of Single And Multimodality Imaging Probes For Pet, Spect And Fluorescence Imaging, Babak Behnam Azad Sep 2011

Development Of Single And Multimodality Imaging Probes For Pet, Spect And Fluorescence Imaging, Babak Behnam Azad

Electronic Thesis and Dissertation Repository

This dissertation is in an integrated format discussing three major projects centered around probe development. In the first project, novel metal-chelated and fluorinated GLP-1 derivatives were prepared all containing D-Ala-8, a modification known to improve resistance towards degradation by dipeptidyl-peptidase IV. The effect of increased distance between DOTA and the peptide chain was investigated using a spacer, in order to reduce steric effects imposed by DOTA. Placement of linker and DOTA moieties were varied within the GLP-1 sequence to test for optimal metal-complex location. Binding affinity of peptide derivatives was determined in vitro with CHO/GLP-1R cell line and shown ...


Nir-Emissive Polymersomal Markers For Molecular-Level Detection Of Metastasis, Wei Qi Aug 2011

Nir-Emissive Polymersomal Markers For Molecular-Level Detection Of Metastasis, Wei Qi

Publicly Accessible Penn Dissertations

Noninvasive imaging technologies, capable of visualizing early carcinoma or dormant or latent metastatic tumor cells and evaluating the efficacy of cancer therapies are becoming increasingly important. In this thesis, NIR-emissive polymersomes are engineered for optimal cellular uptake to enable fluorescence-based tumor targeting. A series of benzothiadiazole conjugated porphyrin oligomers with high emission dipole strength and exceptional large quantum yields in the NIR region are synthesized for optimized emissive output would be greatly enhanced. Furthermore, this thesis established for the first time a class of universal chemistry modification methods to directly attach antibody to polymersomes surface with very high antibody coupling ...


Cell Migration Dynamics After Alteration Of Cell-Cell Contacts In Fibrosarcoma And Glioblastoma Cell Lines, Hassan S. Rizvi, Ronald K. Gary Aug 2011

Cell Migration Dynamics After Alteration Of Cell-Cell Contacts In Fibrosarcoma And Glioblastoma Cell Lines, Hassan S. Rizvi, Ronald K. Gary

Undergraduate Research Opportunities Program (UROP)

Cell migration is a vital component of metastasis. In this study, our intent was to study cell migration by alteration of the Wnt/GSK-3 Pathway. Since BeSO4 is a known GSK-3 kinase inhibitor, we hypothesized that this agent would cause cell migration to decrease as a result of β-catenin stabilization. Two human cell lines, HT-1080 (fibrosarcoma) and A172 (glioblastoma), were used to observe migration levels in the presence and absence of BeSO4. Our results show that cell migration is diminished for cells that were pre-treated with BeSO4, in comparison to the untreated (control) cells.


High Yield Synthesis Of Positron Emission Tomography Ligands For Metabotropic Glutamate Receptor Imaging, Saraanne E. Hitchcock Aug 2011

High Yield Synthesis Of Positron Emission Tomography Ligands For Metabotropic Glutamate Receptor Imaging, Saraanne E. Hitchcock

Student Research Projects, Dissertations, and Theses - Chemistry Department

Positron Emission Tomography (PET) is a powerful and non-invasive imaging technique used for human and animal organ imaging. Currently, the market for PET is project to reach $5.4 billion per year by 2015.5 This research focuses on the direct incorporation of [18F]-fluoride into PET ligands. The widespread use of PET imaging is currently frustrated, in part, by the lack of efficient fluorination chemistry.

Glutamate, one of the 20 most abundant naturally occurring amino acids, serves as a neurotransmitter in the central nervous system. Glutamate functions in this capacity by binding to ionotropic and metabotropic receptors. Metabotropic receptors ...


Application Of Raman Spectroscopy To Lubricants, Lubricated Surfaces And Lubrication Phenomena, David W. Johnson Jul 2011

Application Of Raman Spectroscopy To Lubricants, Lubricated Surfaces And Lubrication Phenomena, David W. Johnson

Chemistry Faculty Publications

Recent advances in lasers and detector technologies and the development of low-cost instruments and fiber-optic probes have brought about an explosion in the lubrication systems being studied by Raman spectroscopy. This article provides examples of the use of Raman spectroscopy in the study of lubrication phenomena, including the characterization of liquid lubricants, lubricant additives, and solid lubricants; the study of vapor-phase lubrication; and the use of coated nanoparticles as lubricants.


Membrane-Dependent Effects Of A Cytoplasmic Helix On The Structure And Drug Binding Of The Influenza Virus M2 Protein, Sarah D. Cady, Tuo Wang, Mei Hong Jun 2011

Membrane-Dependent Effects Of A Cytoplasmic Helix On The Structure And Drug Binding Of The Influenza Virus M2 Protein, Sarah D. Cady, Tuo Wang, Mei Hong

Chemistry Publications

The influenza A M2 protein forms a proton channel for virus infection and also mediates virus assembly and budding. The minimum protein length that encodes both functions contains the transmembrane (TM) domain (roughly residues 22–46) for the amantadine-sensitive proton-channel activity and an amphipathic cytoplasmic helix (roughly residues 45–62) for curvature induction and virus budding. However, structural studies involving the TM domain with or without the amphipathic helix differed on the drug-binding site. Here we use solid-state NMR spectroscopy to determine the amantadine binding site in the cytoplasmic-helix-containing M2(21–61). 13C–2H distance measurements of 13C-labeled protein and ...


Electrochemistry Of Technetium Analogues Rhenium And Molybdenum In Room Temperature Ionic Liquid, Pauline Nancy Serrano Jun 2011

Electrochemistry Of Technetium Analogues Rhenium And Molybdenum In Room Temperature Ionic Liquid, Pauline Nancy Serrano

UNLV Theses, Dissertations, Professional Papers, and Capstones

Rhenium was used as an analog for Technetium to study the electrochemical redox properties because the two elements share the same stable oxidation states in aqueous solutions. However, Tc-99 is radioactive and is not readily available for experimentation purposes. Molybdenum is also of interest because when Mo-99 is irradiated, the decay products are Tc-99m and Tc-99. Approximately 30% Tc-99m is eluted from the Mo columns for radiopharmaceutical use with the remaining Mo-99 source decaying to Tc-99 which is discarded as radioactive hospital waste. Currently there are no viable procedures for the reclamation of the radioactive Tc-99 from either fission streams ...


Genome-Wide Analysis Reveals Padi4 Cooperates With Elk-1 To Activate C-Fos Expression In Breast Cancer Cells., Xuesen Zhang, Matthew J. Gamble, Sonja Stadler, Brian D. Cherrington, Corey P. Causey, Paul R. Thompson, Mark S. Roberson, W Lee Kraus, Scott A. Coonrod Jun 2011

Genome-Wide Analysis Reveals Padi4 Cooperates With Elk-1 To Activate C-Fos Expression In Breast Cancer Cells., Xuesen Zhang, Matthew J. Gamble, Sonja Stadler, Brian D. Cherrington, Corey P. Causey, Paul R. Thompson, Mark S. Roberson, W Lee Kraus, Scott A. Coonrod

Thompson Lab Publications

Peptidylarginine deiminase IV (PADI4) catalyzes the conversion of positively charged arginine and methylarginine residues to neutrally charged citrulline, and this activity has been linked to the repression of a limited number of target genes. To broaden our knowledge of the regulatory potential of PADI4, we utilized chromatin immunoprecipitation coupled with promoter tiling array (ChIP-chip) analysis to more comprehensively investigate the range of PADI4 target genes across the genome in MCF-7 breast cancer cells. Results showed that PADI4 is enriched in gene promoter regions near transcription start sites (TSSs); and, surprisingly, this pattern of binding is primarily associated with actively transcribed ...


Thermochemistry And Bond Energies Of Acetohydrazide, Amides And Cyclic Alkyl Ethers, Sumit Charaya May 2011

Thermochemistry And Bond Energies Of Acetohydrazide, Amides And Cyclic Alkyl Ethers, Sumit Charaya

Theses

Structure, thermochemical properties, bond energies and internal rotation potentials of Acetic Acid Hydrazide (CH3CONHNH2), Acetamide (CH3CONH2) and N-methyl Acetamide (CH3CONHCH3) and their radicals corresponding to loss of hydrogen atom have been studied. Gas phase standard enthalpies of formation and bond energies were calculated using the DFT methods B3LYP/6-31G(d,p), B3LYP/6-31G(2d,2p) and the composite CBS-QB3 methods employing a series of work reactions to further improve accuracy of the ΔHf°(298K). Molecular structures, vibration frequencies and internal rotor potentials were calculated at DFT level. The enthalpies of the parent molecules ...


Synthesis Towards Synthetic Adenosine Receptor, Rajni Gupta May 2011

Synthesis Towards Synthetic Adenosine Receptor, Rajni Gupta

Theses

Adenosine is a biologically important molecule as it acts as local modulator with cytoprotective function in the body. Adenosine accumulates in the extracellular space in response to metabolic stress and cell damage, and elevations in extracellular adenosine level are found in conditions like myocardial ischemia, hypoxia, inflammation and trauma. Its abnormal concentration therefore could be a marker of many diseases. Therefore determining its concentration can help understand the physiological state of the body. However its selective detection by synthetic receptors is not possible till date.

Efforts have been made here to design molecular tweezer for adenosine. Multistep synthesis was done ...


The Synthesis And Biological Evaluation Of Tamandarin B Analogs, Kenneth Lassen May 2011

The Synthesis And Biological Evaluation Of Tamandarin B Analogs, Kenneth Lassen

Publicly Accessible Penn Dissertations

The tamandarin and didemnins are a class of cyclodepsipeptides that have shown a wide range of biological activity. The didemnins have demonstrated antitumor, antiviral and immunosuppressive activity at low nano- and femtomolar levels. Didemnin B was the first marine natural product to enter clinical trials in humans in the United States. The structures of tamandarins A and B were reported in 2000 and possess almost identical structure and biological activity to didemnin B. These compounds have shown impressive biological activity and some progress has been made in establishing structure-activity relationships. However, their molecular mechanism of action is still unclear. The ...


Synthesis Of A Resveratrol Glycinate Derivative., Shelley Marie Van Cleve May 2011

Synthesis Of A Resveratrol Glycinate Derivative., Shelley Marie Van Cleve

Electronic Theses and Dissertations

Recently, the compound resveratrol has had media attention as an anti carcinogen. However, the bioavailability of resveratrol is low in the human system due to its hydrophobic nature. Therefore, it must be administered in high dosages to be effective. A plethora of derivatives have been synthesized that have the potential of resveratrol but sadly share low bioavailability. The first effort of this research was an attempt to produce a more hydrophilic ester of resveratrol. Failing this, the final product was synthesized using a glycine derivative to produce 4-[(1E)-2-(3,5-diacetyloxyphenyl)ethenyl]phenyl N-[(1,1-dimethylethoxy)carbonyl]-glycinate.


Mechanistic Study Of The Small Molecule Inhibitor Dx-52-1, Junru Cui May 2011

Mechanistic Study Of The Small Molecule Inhibitor Dx-52-1, Junru Cui

Master's Theses

Cell migration is a basic biological process that is fundamental to several normal and disease processes such as embryonic development, tissue repair, immune function, angiogenesis and cancer cell invasion and metastasis. Small organic molecules inhibiting cell migration can be used as both research probes and therapeutic agents. DX-52-1, a semisynthetic derivative of the natural product quinocarmycin (also known as quinocarcin), inhibits the migration of Madin-Darby canine kidney epithelial cells with nanomolar concentration. We have identified galectin-3, a multifunctional protein whose best-known function is its sugar binding ability, as a secondary target of DX-52-1 with functions in cell motility. In addition ...


In Vitro Activities Of Synthetic Host Defense Propeptides Processed By Neutrophil Elastase Against Cystic Fibrosis Pathogens., Stephane Desgranges, Florie Le Prieult, Alan Daly, Marian Brennan, Dilip K. Rai, Anusha P. Subasinghage, Chandralal M. Hewage, Sally-Ann Cryan, Catherine M. Greene, Noel G. Mcelvaney, Timothy P. Smyth, Deirdre Fitzgerald-Hughes, Hilary Humphreys, Marc Devocelle May 2011

In Vitro Activities Of Synthetic Host Defense Propeptides Processed By Neutrophil Elastase Against Cystic Fibrosis Pathogens., Stephane Desgranges, Florie Le Prieult, Alan Daly, Marian Brennan, Dilip K. Rai, Anusha P. Subasinghage, Chandralal M. Hewage, Sally-Ann Cryan, Catherine M. Greene, Noel G. Mcelvaney, Timothy P. Smyth, Deirdre Fitzgerald-Hughes, Hilary Humphreys, Marc Devocelle

Chemistry Articles

The antimicrobial and hemolytic activities of a host defense peptide can be controlled by its modification as a propeptide of reduced net charge, which can then be processed by neutrophil elastase, a serine protease involved in chronic airway inflammation and infections associated with cystic fibrosis.


A Sodium Salt Of The Dimer Of Boronoterephthalic Acid Anhydride, Scott Simmons, Albert Fratini, Vladimir Benin Apr 2011

A Sodium Salt Of The Dimer Of Boronoterephthalic Acid Anhydride, Scott Simmons, Albert Fratini, Vladimir Benin

Chemistry Faculty Publications

The title compound, sodium bis­(6-carb­oxy-1-hy­droxy-3-oxo-1,3-dihydro-2,1-benzoxaborol-1-yl)oxidanium, Na+·C16H15B2O13-, was prepared in two steps from 2-bromo-p-xylene. Its crystal structure was determined at 140 K and has triclinic (P) symmetry. The compound presents a unique structural motif, including two units of the cyclic anhydride of boronoterephthalic acid, joined by a protonated, and thereby trivalent, oxonium center. Association in the crystal is realized by complementary hydrogen bonding of the carboxyl groups, as well as by coordination of the sodium cations to the oxygen centers on the five-membered rings.