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Articles 661 - 690 of 779

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Apoptotic And Chemotherapeutic Properties Of Iron (Iii)-Salophene In An Ovarian Cancer Animal Model, Thilo S. Lange, Carolyn Mccourt, Rakesh K. Singh, Kyu Kwang Kim, Ajay P. Singh, Brian S. Luisi, Onur Alptürk, Robert M. Strongin, Laurent Brard Sep 2009

Apoptotic And Chemotherapeutic Properties Of Iron (Iii)-Salophene In An Ovarian Cancer Animal Model, Thilo S. Lange, Carolyn Mccourt, Rakesh K. Singh, Kyu Kwang Kim, Ajay P. Singh, Brian S. Luisi, Onur Alptürk, Robert M. Strongin, Laurent Brard

Chemistry Faculty Publications and Presentations

The cytotoxicity of organometallic compounds iron(III)-, cobalt(III)-, manganese(II)-, and copper(II)-salophene (-SP) on platinum-resistant ovarian cancer cell lines was compared. Fe-SP displayed selective cytotoxicity (IC(50) at ~1 muM) against SKOV-3 and OVCAR-3 cell lines while Co-SP caused cytotoxic effects only at higher concentrations (IC(50) at 60 muM) and Cu-SP effects were negligible. High cytotoxicity of Mn-SP (30-60 muM) appeared to be nonspecific because the Mn-chloride salt reduced cell viability similarly. The effect of Fe-SP at 1 muM proved to be ovarian cancer cell selective when compared to a panel of cell lines derived from ...


Hypericum In Infection: Identification Of Anti-Viral And Anti-Inflammatory Constituents, Diane F. Birt, Mark P. Widrlechner, Kimberly D.P. Hammer, Matthew L. Hillwig, Jingqiang Wei, George A. Kraus, Patricia A. Murphy, Joe-Ann Mccoy, Eve S. Wurtele, Jeffrey D. Neighbors, David F. Wiemer, Wendy J. Maury, Jason P. Price Aug 2009

Hypericum In Infection: Identification Of Anti-Viral And Anti-Inflammatory Constituents, Diane F. Birt, Mark P. Widrlechner, Kimberly D.P. Hammer, Matthew L. Hillwig, Jingqiang Wei, George A. Kraus, Patricia A. Murphy, Joe-Ann Mccoy, Eve S. Wurtele, Jeffrey D. Neighbors, David F. Wiemer, Wendy J. Maury, Jason P. Price

Food Science and Human Nutrition Publications

The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum, and Prunella botanical supplements for human-health benefit, emphasizing anti-viral, anti-inflammatory, and anti-pain activities. This mini-review reports on ongoing studies on Hypericum. The Center uses the genetically diverse, well-documented Hypericum populations collected and maintained at the USDA-ARS North Central Regional Plant Introduction Station (NCRPIS), and the strength of research in synthetic chemistry at Iowa State University to tap natural diversity, to help discover key constituents and interactions among constituents that impact bioactivity and toxicity. The NCRPIS has acquired more than 180 distinct populations of Hypericum, with a ...


Structure And Function Of The Influenza A M2 Proton Channel, Sarah D. Cady, Wenbin Luo, Fanghao Hu, Mei Hong Jun 2009

Structure And Function Of The Influenza A M2 Proton Channel, Sarah D. Cady, Wenbin Luo, Fanghao Hu, Mei Hong

Chemistry Publications

The M2 protein of influenza A viruses forms a tetrameric pH-activated proton-selective channel that is targeted by the amantadine class of antiviral drugs. Its ion channel function has been extensively studied by electrophysiology and mutagenesis; however, the molecular mechanism of proton transport is still elusive, and the mechanism of inhibition by amantadine is controversial. We review the functional data on proton channel activity, molecular dynamics simulations of the proton conduction mechanism, and high-resolution structural and dynamical information of this membrane protein in lipid bilayers and lipid-mimetic detergents. These studies indicate that elucidation of the structural basis of M2 channel activity ...


Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess May 2009

Identifying Biomarkers For Resistance To Novel Cisplatin Analogues In Human Lung, Breast And Prostate Cancers, Becky Michelle Hess

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cisplatin is a common therapeutic agent used in cancer treatment. Unfortunately, resistance to cisplatin in addition to severe side effects limits its use in cancer treatment. Two novel cisplatin analogues, 4DB and 4TB were shown to have varying cytotoxicity in lung, breast and prostate cancer cells. The hypothesis for this study states that the differences in 4DB and 4TB cytotoxicity among different tissue types is due to the type and efficiency of DNA repair mechanisms involved in response to these drugs.

To test the hypothesis, proteins involved in the rate limiting step of nucleotide excision repair (NER) and mismatch repair ...


Preparation And Characterization Of Some Substituted Benzyl N-Nitrosocarbamates Containing An N-2-(Methylthio)Ethyl Or A Bis(2-Aminoethyl)Sulfide Functionality, Satya Venkata, Eric Shamo, Vladimir Benin Jan 2009

Preparation And Characterization Of Some Substituted Benzyl N-Nitrosocarbamates Containing An N-2-(Methylthio)Ethyl Or A Bis(2-Aminoethyl)Sulfide Functionality, Satya Venkata, Eric Shamo, Vladimir Benin

Chemistry Faculty Publications

The synthesis and characterization of some substituted benzyl N-nitrosocarbamates with an N-2-(methylthio)ethyl or a bis(2-aminoethyl)sulfide functionality is reported, as a part of a long-term goal to design and prepare novel photolabile structures that could be used as substances for controlled release of alkylating and/or crosslinking agents. The synthesis was accomplished by reaction of benzyl chloroformates with the corresponding amines, resulting in the preparation of carbamates. The latter were subsequently nitrosated, utilizing two different N-nitrosation methods, to yield the target structures.


Androgen-Stimulated Udp-Glucose Dehydrogenase Expression Limits Prostate Androgen Availability Without Impacting Hyaluronan Levels, Qin Wei, Robert Galbenus, Ashraf Raza, Ronald Cerny, Melanie A. Simpson Jan 2009

Androgen-Stimulated Udp-Glucose Dehydrogenase Expression Limits Prostate Androgen Availability Without Impacting Hyaluronan Levels, Qin Wei, Robert Galbenus, Ashraf Raza, Ronald Cerny, Melanie A. Simpson

Ronald Cerny Publications

UDP-glucose dehydrogenase (UGDH) oxidizes UDP-glucose to UDP-glucuronate, an essential precursor for production of hyaluronan (HA), proteoglycans, and xenobiotic glucuronides. High levels of HA turnover in prostate cancer are correlated with aggressive progression. UGDH expression is high in the normal prostate even though HA accumulation is virtually undetectable. Thus, its normal role in the prostate may be to provide precursors for glucuronosyltransferase enzymes, which inactivate and solubilize androgens by glucuronidation. In this report, we quantified androgen dependence of UGDH, glucuronosyltransferase, and HA synthase expression. Androgen dependent and independent human prostate cancer cell lines were used to test the effects of UGDH ...


Generation Of Novel Pikromycin Antibiotic Products Through Mutasynthesis, Shuchi Gupta, Venkatraman Lakshmanan, Beom Seok Kim, Robert Fecik, Kevin A. Reynolds Jan 2009

Generation Of Novel Pikromycin Antibiotic Products Through Mutasynthesis, Shuchi Gupta, Venkatraman Lakshmanan, Beom Seok Kim, Robert Fecik, Kevin A. Reynolds

Chemistry Faculty Publications and Presentations

Mutasynthesis in pikromycin PKS: The amenability of pikromycin polyketide synthase to mutational biosynthesis has been demonstrated. A natural triketide and its analogues, activated as N-acetyl-cysteamine thioesters, were synthesized and fed to a pikAI-deleted strain; this led to the production of new antibiotics. A vinyl analogue was found to have better antibacterial activity than pikromycin.


A Multi-Step Nmr Screen For The Identification And Evaluation Of Chemical Leads For Drug Discovery, Kelly A. Mercier, Matthew D. Shortridge, Robert Powers Jan 2009

A Multi-Step Nmr Screen For The Identification And Evaluation Of Chemical Leads For Drug Discovery, Kelly A. Mercier, Matthew D. Shortridge, Robert Powers

Faculty Publications -- Chemistry Department

A multi-step NMR based screening assay is described for identifying and evaluating chemical leads for their ability to bind a target protein. The multi-step NMR assay provides structure-related information while being an integral part of a structure based drug discovery and design program. The fundamental principle of the multi-step NMR assay is to combine distinct 1D and 2D NMR techniques, in such a manner, that the inherent strengths and weakness associated with each technique is complementary to each other in the screen. By taking advantage of the combined strengths of 1D and 2D NMR experiments, it is possible to minimize ...


Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar Jan 2009

Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar

Pharmacy Faculty Articles and Research

A specific and sensitive liquid chromatography (LC)-tandem mass spectrometric method for quantitative determination of methylprednisolone (MP) in rat plasma and liver was developed and validated using triamcinolone acetonide as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma and liver. The separation of MP was performed on a C(18) column with a mobile phase of acetonitrile:0.5% formic acid aqueous solution (85:15, v/v) over 4 min. The assay was based on the selected reaction monitoring transitions at m/z 375 -> 161 for MP ...


Immobilization Method For Producing Active Α1-Acid Glycoprotein, David S. Hage, Hai Xuan Jan 2009

Immobilization Method For Producing Active Α1-Acid Glycoprotein, David S. Hage, Hai Xuan

Faculty Publications -- Chemistry Department

A method and kit for immobilization of a glycoprotein. The method may include activating an affinity Support. The affinity Support may be activated by reacting the affinity Support with a compound that is reactive with one or more functional groups included within the glycoprotein. The method may also include oxidizing the glycoprotein in which oxidation conditions are selected to yield an oxidized glycoprotein that is biologically active and contains a Sufficient number of reactive aldehyde groups for coupling to a Support. For example, the oxidized glycoprotein may include five reactive aldehyde groups. In addition, the method may include reacting the ...


Anhydrous Fluoride Salts And Reagents And Methods For Their Production, Stephen G. Dimagno, Haoran Sun Jan 2009

Anhydrous Fluoride Salts And Reagents And Methods For Their Production, Stephen G. Dimagno, Haoran Sun

Faculty Publications -- Chemistry Department

Anhydrous organic fluoride salts and reagents prepared by a method comprising the nucleophilic Substitution of a fluorinated aromatic or fluorinated unsaturated organic compound with a salt having the formula: [QnM]x+Ax- in an inert polar, aprotic solvent; wherein M is an atom capable of supporting a formal positive charge, the n groups Q are independently varied organic moieties, n is an integer such that the [QnM] carries at least one formal positive charge, x is an integer defining the number of formal positive charge(s), +, carried by the [QnM], A- is an ...


Controlled Assembly Of Rodlike Viruses With Polymers, T. Li, L. Wu, N. Suthiwangcharoen, M. A. Bruckman, D. Cash, J. S. Hudson, Soumitra Ghoshroy, Qian Wang Jan 2009

Controlled Assembly Of Rodlike Viruses With Polymers, T. Li, L. Wu, N. Suthiwangcharoen, M. A. Bruckman, D. Cash, J. S. Hudson, Soumitra Ghoshroy, Qian Wang

Faculty Publications

A practical method to assemble rodlike tobacco mosaic virus and bacteriophage M13 with polymers was developed, which afforded a 3D core–shell composite with morphological control.


Synthesis Of Facial Amphiphile 3,7-Diamino-5Α-Cholestane Derivatives As A Molecular Receptor, Md Wasi Ahmad, Young Mee Jung, Sharaf Nawaz Khan, Hong Seok Kim Dec 2008

Synthesis Of Facial Amphiphile 3,7-Diamino-5Α-Cholestane Derivatives As A Molecular Receptor, Md Wasi Ahmad, Young Mee Jung, Sharaf Nawaz Khan, Hong Seok Kim

Dr. Mohammad Wasi Ahmad (Md Wasi Ahmad)

A series of facial amphiphiles 3,7-diaminocholestane were synthesized from 3,7-diketocholestane via 2 sequential reductive aminations and anion recognition was evaluated with acetate, chloride, bromide, fluoride and phosphate anions. The stereo-selective reductive amination protocol was utilized to synthesized facial amphiphiles afforded receptors in high yields. The molecular receptor 2 showed the highest binding constant with acetate in a 1:1 ratio.


Examination Of An Aloe Vera Galacturonate Polysaccharide Capable Of In Situ Gelation For The Controlled Release Of Protein Therapeutics, Shawn David Mcconaughy Dec 2008

Examination Of An Aloe Vera Galacturonate Polysaccharide Capable Of In Situ Gelation For The Controlled Release Of Protein Therapeutics, Shawn David Mcconaughy

Dissertations

A therapeutic delivery platform has been investigated with the ultimate goal of designing a sustained protein release matrix utilizing an in-situ gelling, acidic polysaccharide derived from the Aloe vera plant. The Aloe vera polysaccharide (AvP) has been examined in order to determine how chemical composition, structure, molecular weight and solution behavior affect gelation and protein/peptide delivery. Correlations are drawn between structural characteristics and solution behavior in order to determine the impact of polymer conformation and solvation on gel formation under conditions designed to simulate nasal applications. Steady state and dynamic rheology, classic and dynamic light scattering, zeta potential, pulse ...


A Study On The Protein Interaction With Different Platinum Compounds, Nayna Kotadia Jul 2008

A Study On The Protein Interaction With Different Platinum Compounds, Nayna Kotadia

Masters Theses & Specialist Projects

Since the discovery of anti-tumor activity of cisplatin in 1960, significant progress has been made in treating metastatic or advanced cancer with cisplatin and platinum compounds. Platinum compounds covalently bind to DNA and disrupt DNA function. They are also known to bind with amino acids like methionine, histidine and cysteine to form cisplatin-protein adducts which are responsible for most of its cytotoxicity and side effects. Recent articles on cisplatin-protein have shown that adding bulky adjuncts to cisplatin or using different platinum compounds varies the degree and extent of reaction thus possibly reducing cisplatin resistance and side effects.

One of the ...


Preparation Of Halogenated Derivatives Of Thiazolo[5,4-D]Thiazole Via Direct Electrophilic Aromatic Substitution, Vladimir Benin, Alan T. Yeates, Douglas Dudis May 2008

Preparation Of Halogenated Derivatives Of Thiazolo[5,4-D]Thiazole Via Direct Electrophilic Aromatic Substitution, Vladimir Benin, Alan T. Yeates, Douglas Dudis

Chemistry Faculty Publications

Chlorination and bromination reactions of thiazolo[5,4-d]thiazole led to the generation of its mono- and dihalogenated derivatives. These are the first instances of successful direct electrophilic aromatic substitution in the thiazolo[5,4-d]thiazole ring system. X-ray analysis demonstrates that both 2-bromothiazolo[5,4-d]-thiazole and 2,5-dibromothiazolo[5,4-d]thiazole are planar structures, with strongly manifested π-stacking in the solid state. Theoretical analysis of the pyridine-catalyzed halogenation (MP2/6-31+G(d) and B3LYP/6-31+G(d)calculations) reveals that introduction of one halogen actually leads to a slightly enhanced reactivity towards further halogenation ...


Iron(Iii)-Salophene: An Organometallic Compound With Selective Cytotoxic And Anti-Proliferative Properties In Platinum-Resistant Ovarian Cancer Cells, Thilo S. Lange, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Carolyn Mccourt, Laurent Brard May 2008

Iron(Iii)-Salophene: An Organometallic Compound With Selective Cytotoxic And Anti-Proliferative Properties In Platinum-Resistant Ovarian Cancer Cells, Thilo S. Lange, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Carolyn Mccourt, Laurent Brard

Chemistry Faculty Publications and Presentations

Background: In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovariancancer cell lines were investigated.

Methodology/Principal Findings: Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 μM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented ...


Second-Sphere Amino Acids Contribute To Transition-State Structure In Bovine Purine Nucleoside Phosphorylase, Lei Li, Minkui Luo, Mahmoud Ghanem, Erika A. Taylor, Vern L. Schramm Feb 2008

Second-Sphere Amino Acids Contribute To Transition-State Structure In Bovine Purine Nucleoside Phosphorylase, Lei Li, Minkui Luo, Mahmoud Ghanem, Erika A. Taylor, Vern L. Schramm

Erika A. Taylor, Ph.D.

Transition-state structures of human and bovine of purine nucleoside phosphorylases differ, despite 87% homologous amino acid sequences. Human PNP (HsPNP) has a fully dissociated transition state, while that for bovine PNP (BtPNP) has early SN1 character. Crystal structures and sequence alignment indicate that the active sites of these enzymes are the same within crystallographic analysis, but residues in the second-sphere from the active sites differ significantly. Residues in BtPNP have been mutated toward HsPNP, resulting in double (Asn123Lys; Arg210Gln) and triple mutant PNPs (Val39Thr; Asn123Lys; Arg210Gln). Steady-state kinetic studies indicated unchanged catalytic activity, while pre-steady-state studies indicate that the chemical ...


C–N Bond Rotation And E–Z Isomerism In Some N-Benzyl-N-Methylcarbamoyl Chlorides: A Dft Study, Michael Horwath, Vladimir Benin Feb 2008

C–N Bond Rotation And E–Z Isomerism In Some N-Benzyl-N-Methylcarbamoyl Chlorides: A Dft Study, Michael Horwath, Vladimir Benin

Chemistry Faculty Publications

The current report presents the first theoretical study of the restricted CN bond rotation in carbamoyl chlorides. Several N-benzyl-N-methylcarbamoyl chlorides were investigated, with varying pattern of substitution in the aromatic ring. Optimizations and frequency calculations were conducted employing DFT at the B3LYP/6-31+G(d) level of theory. Each of the studied structures exhibits a pair of rotamers (s-Z and s-E), generated upon rotation around the C(O)N bond. The s-E isomer is the global minimum in every case, but the preference for it is usually less than 1 kcal/mol. Two possible ...


Echinacea In Infection1–4, Diane F. Birt, Mark P. Widrlechner, Carlie A. Lalone, Lankun Wu, Jaehoon Bae, Avery K S Solco, George A. Kraus, Patricia A. Murphy, Eve S. Wurtele, Qiang Leng, Steven C. Hebert, Wendy J. Maury, Jason P. Price Feb 2008

Echinacea In Infection1–4, Diane F. Birt, Mark P. Widrlechner, Carlie A. Lalone, Lankun Wu, Jaehoon Bae, Avery K S Solco, George A. Kraus, Patricia A. Murphy, Eve S. Wurtele, Qiang Leng, Steven C. Hebert, Wendy J. Maury, Jason P. Price

Genetics, Development and Cell Biology Publications

Ongoing studies have developed strategies for identifying key bioactive compounds and chemical profiles in Echinacea with the goal of improving its human health benefits. Antiviral and antiinflammatory–antipain assays have targeted various classes of chemicals responsible for these activities. Analysis of polar fractions of E. purpurea extracts showed the presence of antiviral activity, with evidence suggesting that polyphenolic compounds other than the known HIV inhibitor, cichoric acid, may be involved. Antiinflammatory activity differed by species, with E. sanguinea having the greatest activity and E. angustifolia, E. pallida, and E. simulata having somewhat less. Fractionation and studies with pure compounds indicate ...


Monohydroxamic Acids And Bridging Dihydroxamic Acids As Chelators To Ruthenium(Iii) And As Nitric Oxide Donors: Syntheses, Speciation Studies And Nitric Oxide Releasing Investigations., Darren M. Griffith, Krystyna Krot, Jedd Comiskey, Kevin B. Nolan, Celine J. Marmion Jan 2008

Monohydroxamic Acids And Bridging Dihydroxamic Acids As Chelators To Ruthenium(Iii) And As Nitric Oxide Donors: Syntheses, Speciation Studies And Nitric Oxide Releasing Investigations., Darren M. Griffith, Krystyna Krot, Jedd Comiskey, Kevin B. Nolan, Celine J. Marmion

Chemistry Articles

The synthesis and spectroscopic characterisation of novel mononuclear Ru(III)(edta)(hydroxamato) complexes of general formula [Ru(H2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-C1 and 3-Me-phenylhydroxamato), as well as the first example of a Ru(III)-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)].H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear Ru(III) complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(mu-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with Ru(III), are also described. The speciation of all of these systems (with the exception of the ...


N-Acetyl-2-Hydroxy-N '- Methoxy(1-Methylindol-2-Yl)Methyl Benzohydrazide, Azhar Ariffin, Ng S. W., Yehye W. A., Rahman N. A. Jan 2008

N-Acetyl-2-Hydroxy-N '- Methoxy(1-Methylindol-2-Yl)Methyl Benzohydrazide, Azhar Ariffin, Ng S. W., Yehye W. A., Rahman N. A.

Azhar Ariffin

In the crystal structure of the title Schiff-base, C(20)H(21)N(3)O(4), the amino group forms an N-H center dot center dot center dot O hydrogen bond to the acetyl group of an adjacent molecule, forming a zigzag chain. The 2-hydroxy group is internally hydrogen bonded to the amido group though an O-H center dot center dot center dot O hydrogen bond.


Identification And Analysis Of Prohibitin In B16 Mouse Melanoma Cells, Christopher Francis Jan 2008

Identification And Analysis Of Prohibitin In B16 Mouse Melanoma Cells, Christopher Francis

Theses, Dissertations and Capstones

Prohibitin, a highly conserved protein found in eukaryotic cells, has been found in recent years to possess a wide variety of functions in the cell. Whereas the mechanisms by which the protein functions are still largely unknown, it is clear that prohibitin possesses very strong anti-proliferative properties in the cell, as well as potentially both nuclear and mitochondrial functions based upon its movement and localization upon apoptotic signaling. Upon treatment with retinoic acid, transformed B16 mouse melanoma cells also indicate a differential expression of prohibitin in which production of the protein is increased. The purpose of this work was to ...


Antimalarial Activity Of 2,4-Diaminopyrimidines, J. Morgan, R. Haritakul, Paul A. Keller Jan 2008

Antimalarial Activity Of 2,4-Diaminopyrimidines, J. Morgan, R. Haritakul, Paul A. Keller

Faculty of Science - Papers (Archive)

A series of 2,4- and 4,6-diaminopyrimidines were prepared and evaluated for their in vitro antimalarial activity. Of the 12 compounds tested 7 showed reasonable activity with 1 having a sub-micromolar IC50.


New Cyclic Peptides Via Ring-Closing Metathesis Reactions And Their Anti-Bacterial Activities, Timothy P. Boyle, John B. Bremner, Jonathan Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, David I. Rhodes Jan 2008

New Cyclic Peptides Via Ring-Closing Metathesis Reactions And Their Anti-Bacterial Activities, Timothy P. Boyle, John B. Bremner, Jonathan Coates, John Deadman, Paul A. Keller, Stephen G. Pyne, David I. Rhodes

Faculty of Science - Papers (Archive)

As part of a program investigating cyclic peptides with an internal aromatic hydrophobic scaffold as potential novel anti-bacterial agents, we explored the synthesis of simple tyrosine-based systems. These were prepared via key intermediates containing internal allylglycine and allyltyrosine residues for subsequent ring closing metathesis reactions. Although the resulting anti-bacterial activity against Staphylococcus aureus was modest, this represents a novel and simple route to this class of compounds. One intermediate acyclic dipeptide precursor showed good activity against S. aureus with an MIC of 7.8 µg/mL.


Functional Cloning And Characterization Of The Multidrug Efflux Pumps Norm From Neisseria Gonorrhoeae And Ydhe From Escherichia Coli, Feng Long, Corrinne Rouquette-Loughlin, William M. Shafer, Edward Yu Jan 2008

Functional Cloning And Characterization Of The Multidrug Efflux Pumps Norm From Neisseria Gonorrhoeae And Ydhe From Escherichia Coli, Feng Long, Corrinne Rouquette-Loughlin, William M. Shafer, Edward Yu

Physics and Astronomy Publications

Active efflux of antimicrobial agents is one of the most important adapted strategies that bacteria use to defend against antimicrobial factors that are present in their environment. The NorM protein of Neisseria gonorrhoeae and the YdhE protein of Escherichia coli have been proposed to be multidrug efflux pumps that belong to the multidrug and toxic compound extrusion (MATE) family. In order to determine their antimicrobial export capabilities, we cloned, expressed, and purified these two efflux proteins and characterized their functions both in vivo and in vitro. E. coli strains expressing norM or ydhE showed elevated (twofold or greater) resistance to ...


Conformational Change Of The Acrr Regulator Reveals A Possible Mechanism Of Induction, Ruoyu Gu, Ming Li, Chih-Chia Su, Feng Long, Matthew D. Routh, Feng Yang, Gerry Mcdermott, Edward Yu Jan 2008

Conformational Change Of The Acrr Regulator Reveals A Possible Mechanism Of Induction, Ruoyu Gu, Ming Li, Chih-Chia Su, Feng Long, Matthew D. Routh, Feng Yang, Gerry Mcdermott, Edward Yu

Physics and Astronomy Publications

The Escherichia coli AcrR multidrug-binding protein represses transcription of acrAB and is induced by many structurally unrelated cytotoxic compounds. The crystal structure of AcrR in space group P2221 has been reported previously. This P2221 structure has provided direct information about the multidrug-binding site and important residues for drug recognition. Here, a crystal structure of this regulator in space group P31 is presented. Comparison of the two AcrR structures reveals possible mechanisms of ligand binding and AcrR regulation.


Crystallization And Preliminary X-Ray Diffraction Analysis Of The Multidrug Efflux Transporter Norm From Neisseria Gonorrhoeae, Chih-Chia Su, Feng Long, Gerry Mcdermott, William M. Shafer, Edward Yu Jan 2008

Crystallization And Preliminary X-Ray Diffraction Analysis Of The Multidrug Efflux Transporter Norm From Neisseria Gonorrhoeae, Chih-Chia Su, Feng Long, Gerry Mcdermott, William M. Shafer, Edward Yu

Physics and Astronomy Publications

The crystallization and preliminary X-ray data analysis of the NorM multidrug efflux pump produced by Neisseria gonorrhoeae are reported. NorM is a cytoplasmic membrane protein that consists of 459 amino-acid residues. It is a member of the recently classified multidrug and toxic compound extrusion (MATE) family of transporters and recognizes a number of cationic toxic compounds such as ethidium bromide, acriflavin, 2-N-methylellipticinium and ciprofloxacin. Recombinant NorM protein was expressed in Escherichia coli and purified by metal-affinity and gel-filtration chromatography. The protein was crystallized using hanging-drop vapor diffusion. X-ray diffraction data were collected from cryocooled crystals at a synchrotron ...


Reduced Acute Inflammatory Responses To Microgel Conformal Coatings, Amanda W. Bridges, Neetu Singh, Kellie L. Burns, Julia E. Babensee, L. Andrew Lyon, Andrés J. García Jan 2008

Reduced Acute Inflammatory Responses To Microgel Conformal Coatings, Amanda W. Bridges, Neetu Singh, Kellie L. Burns, Julia E. Babensee, L. Andrew Lyon, Andrés J. García

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Implantation of synthetic materials into the body elicits inflammatory host responses that limit medical device integration and biological performance. This inflammatory cascade involves protein adsorption, leukocyte recruitment and activation, cytokine release, and fibrous encapsulation of the implant. We present a coating strategy based on thin films of poly(N-isopropylacrylamide) hydrogel microparticles (i.e. microgels) cross-linked with poly(ethylene glycol) diacrylate. These particles were grafted onto a clinically relevant polymeric material to generate conformal coatings that significantly reduced in vitro fibrinogen adsorption and primary human monocyte/macrophage adhesion and spreading. These microgel coatings also reduced leukocyte adhesion and expression of pro-inflammatory ...


Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon Jan 2008

Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for ...