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Low-molecular-weight Compounds (low-molecular-weight + compound)
Selected AbstractsGeneration of Compositional-Gradient Structures in Biodegradable, Immiscible, Polymer Blends by Intermolecular Hydrogen-Bonding Interactions,ADVANCED FUNCTIONAL MATERIALS, Issue 10 2005B. Hexig Abstract A biodegradable, immiscible poly(butylenes adipate- co -butylenes terephthalate) [P(BA- co -BT)]/poly(ethylene oxide) (PEO) polymer blend film with compositional gradient in the film-thickness direction has been successfully prepared in the presence of a low-molecular-weight compound 4,4,-thiodiphenal (TDP), which is used as a miscibility-enhancing agent. The miscibilities of the P(BA- co -BT)/PEO/TDP ternary blend films and the P(BA- co -BT)/PEO/TDP gradient film were investigated by differential scanning calorimetry (DSC). The compositional gradient structure of the P(BA- co -BT)/PEO/TDP (46/46/8 w/w/w) film has been confirmed by microscopic mapping measurement of Fourier-transform infrared spectra and dynamic mechanical thermal analysis. We have developed a new strategy for generating gradient-phase structures in immiscible polymer-blend systems by homogenization, i.e., adding a third agent that can enhance the miscibility of the two immiscible polymers through simultaneous formation of hydrogen bonds with two component polymers. [source] Structure-assisted discovery of an aminothiazole derivative as a lead molecule for inhibition of bacterial fatty-acid synthesisACTA CRYSTALLOGRAPHICA SECTION D, Issue 12 2007Günter Pappenberger Fatty-acid synthesis in bacteria is of great interest as a target for the discovery of antibacterial compounds. The addition of a new acetyl moiety to the growing fatty-acid chain, an essential step in this process, is catalyzed by ,-ketoacyl-ACP synthase (KAS). It is inhibited by natural antibiotics such as cerulenin and thiolactomycin; however, these lack the requirements for optimal drug development. Structure-based biophysical screening revealed a novel synthetic small molecule, 2-phenylamino-4-methyl-5-acetylthiazole, that binds to Escherichia coli KAS I with a binding constant of 25,µM as determined by fluorescence titration. A 1.35,Ĺ crystal structure of its complex with its target reveals noncovalent interactions with the active-site Cys163 and hydrophobic residues of the fatty-acid binding pocket. The active site is accessible through an open conformation of the Phe392 side chain and no conformational changes are induced at the active site upon ligand binding. This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. The structural information on the protein,ligand interaction offers strategies for further optimization of this low-molecular-weight compound. [source] Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical haptenCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2009C. B. Mathias Summary Background Occupational exposure to chemicals is an important cause of asthma. Recent studies indicate that IgE antibodies enhance sensitization to chemicals in the skin. Objective We investigated whether IgE might similarly promote the development of airway inflammation following inhalation of a contact sensitizer. Methods A model of chemical-induced asthma is described in which introduction of the low-molecular-weight compound, trinitrobenzene sulphonic acid (TNBS), via the respiratory tract was used for both sensitization and challenge. The role of IgE antibodies in the immune response to inhaled TNBS in this model was assessed by comparing the responses of wild-type (WT) and IgE-deficient (IgE,/,) mice on the BALB/c background. Reconstitution of circulating IgE levels by intravenous injection of IgE antibodies into IgE,/, mice before sensitization was performed to confirm the role of IgE in any differences observed between the responses of WT and IgE,/, mice. Results Intranasal challenge of TNBS-sensitized (but not sham-sensitized control mice) induced intense pulmonary inflammation. Macrophages, eosinophils and lymphocytes, including T, B, natural killer and natural killer T cells, were recruited to the airway and the animals displayed bronchial hyperresponsiveness (BHR) to methacholine. Serum levels of murine mast cell protease-1 (mMCP-1) were elevated suggesting mast cell activation. In contrast, the development of airway inflammation, recruitment of lymphocytes, induction of BHR and production of mMCP-1 were all significantly attenuated in IgE-deficient mice. Reconstitution of IgE,/, mice with IgE (of unrelated antigen specificity) before sensitization partially restored these features of asthma. Conclusion Our data indicate that IgE antibodies non-specifically enhance the development of airway inflammation induced by exposure to chemical antigens. [source] Partition Behavior of Polycyclic Aromatic Hydrocarbons Between Aged Coal Tar and Water,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2009Lihua Liu Abstract Coal tar aged in a large-scale, artificial aquifer experiment for five years was subsequently investigated for leaching behavior of polycyclic aromatic hydrocarbons (PAHs). After five years, the initially liquid coal tar had solidified and formed segregated particles with a grain size similar to that of the sandy aquifer material. The composition of the aged coal tar (ACT) with regard to PAHs was remarkably different from that of the original bulk coal tar (BCT), because most of the low-molecular-weight compounds had been depleted. Equilibrium aqueous-phase concentrations of 17 PAHs leaching from the aquifer material containing the ACT were measured from consecutive equilibration steps at increasing temperatures of between 25 and 100C using accelerated solvent extraction. The results showed 2-to 5,000-fold lower concentrations than those from BCT, indicating dramatic changes of dissolution behavior of PAHs from coal tar after the five-year aging period. Predictions based on Raoult's law with the subcooled liquid solubilities substantially overestimated the equilibrium aqueous-phase concentrations of the PAHs from ACT, whereas the estimations were reasonable if the solid solubilities were employed instead. The enthalpies of phase transfer from ACT to water were determined based on the van't Hoff equation. The resulting values agreed with the dissolution enthalpies of pure solid rather than subcooled liquid PAHs. [source] Radiotracer-based method for determining water solubility of highly insoluble compoundsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2006Ketai Wang Abstract Ascertaining the aqueous solubility of compounds is important in the selection of drug candidates. We describe a radiotracer method for estimating water solubility of compounds that are soluble in dimethyl sulfoxide (DMSO). Various volumes of DMSO, saturated with 127I-labeled compound and spiked with the corresponding 125I-labeled derivative, are mixed in de-ionized water and the tubes centrifuged to remove insoluble material. Since (i) the iodine-127 and iodine-125 compounds have the same solubilities and are equally distributed in the DMSO,water solution, and (ii) the nonradioactive compound is accurately weighed, dissolved in a known volume of DMSO, and then further diluted as required, the concentration of compound in solution can be calculated and plotted as a function of the DMSO-to-water ratio. Water solubility of the compound is then determined by extrapolation of the linear fit of data points to zero DMSO. As proof of the methodology, 5-iodo-2,-deoxyuridine (IUdR) and 2-iodo-8-methyl-8H -quino[4,3,2- kl]acridine (IMAc), water-soluble compounds, were assessed using 125IUdR and 125IMAc, respectively. The solubility values obtained by the radiotracer method were similar to those acquired by spectrophotometry. Values calculated for several water-insoluble compounds indicate that the radiotracer method can accurately quantify the solubility of low-molecular-weight compounds (1000,2000 Da) in the pg,ng/ml range. Copyright © 2006 John Wiley & Sons, Ltd. [source] Monolithic poly(1,2-bis(p -vinylphenyl)ethane) capillary columns for simultaneous separation of low- and high-molecular-weight compoundsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 15-16 2009Andreas Greiderer Abstract Monolithic poly(1,2-bis(p -vinylphenyl)ethane (BVPE)) capillary columns were prepared by thermally initiated free radical polymerisation of 1,2-bis(p -vinylphenyl)ethane in the presence of inert diluents (porogens) and ,,,,-azoisobutyronitrile (AIBN) as initiator. Polymerisations were accomplished in 200 ,m ID fused silica capillaries at 65°C and for 60 min. Mercury intrusion porosimetry measurements of the polymeric RP support showed a broad bimodal pore-size-distribution of mesopores and small macropores in the range of 5,400 nm and flow-channels in the ,m range. N2 -adsorption (BET) analysis resulted in a tremendous enhancement of surface area (101 m2/g) of BVPE stationary phases compared to typical organic monoliths (,20 m2/g), indicating the presence of a considerable amount of mesopores. Consequently, the adequate proportion of both meso- and (small) macropores allowed the rapid and high-resolution separation of low-molecular-weight compounds as well as biomolecules on the same monolithic support. At the same time, the high fraction of flow-channels provided enhanced column permeability. The chromatographic performance of poly(1,2-bis(p -vinylphenyl)ethane) capillary columns for the separation of biomolecules (proteins, oligonucleotides) and small molecules (alkyl benzenes, phenols, phenons) are demonstrated in this article. Additionally, pressure drop versus flow rate measurements of novel poly(1,2-bis(p -vinylphenyl)ethane) capillary columns confirmed high mechanical robustness, low swelling in organic solvents and high permeability. Due to the simplicity of monolith fabrication, comprehensive studies of the retention and separation behaviour of monolithic BVPE columns resulted in high run-to-run and batch-to-batch reproducibilities. All these attributes prove the excellent applicability of monolithic poly(1,2-bis(p -vinylphenyl)ethane) capillary columns for ,-HPLC towards a huge range of analytes of different chemistries and molecular sizes. [source] Radical scavenging activities, endogenous oxidative enzymes and total phenols in edible mushrooms commonly consumed in EuropeJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 12 2007Ana Cristina Ramírez-Anguiano Abstract Edible mushrooms are a good source of antioxidants. Methanol extracts of mushrooms such as Pleurotus sp., Agaricus bisporus, Morchella esculenta, Boletus edulis (approx. 2 mg mL,1) showed a high 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity close to 90%. Water extracts showed even higher antioxidant activity. In this case, B. edulis, Lentinus edodes and Amanita cesarea showed the highest 2,2,-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging activity at approx. 0.14 mg mL,1. Other mushrooms such as Lactarius deliciosus and Cantharellus cibarius showed lower antioxidant activity in both extracts. Oxidative enzymes (peroxidases and polyphenol oxidases) present in the water fractions reduced their antioxidant activity by different extents since the phenols responsible for the antioxidant activity were not only those substrates of the oxidative enzymes. Other phenolic compounds and low-molecular-weight compounds were also involved in the antioxidant activity and differed depending on mushroom species. Copyright © 2007 Society of Chemical Industry [source] Botrytis cinerea: the cause of grey mould diseaseMOLECULAR PLANT PATHOLOGY, Issue 5 2007BRIAN WILLIAMSON SUMMARY Introduction:,Botrytis cinerea (teleomorph: Botryotinia fuckeliana) is an airborne plant pathogen with a necrotrophic lifestyle attacking over 200 crop hosts worldwide. Although there are fungicides for its control, many classes of fungicides have failed due to its genetic plasticity. It has become an important model for molecular study of necrotrophic fungi. Taxonomy:, Kingdom: Fungi, phylum: Ascomycota, subphylum: Pezizomycotina, class: Leotiomycetes, order: Helotiales, family: Sclerotiniaceae, genus: Botryotinia. Host range and symptoms: Over 200 mainly dicotyledonous plant species, including important protein, oil, fibre and horticultural crops, are affected in temperate and subtropical regions. It can cause soft rotting of all aerial plant parts, and rotting of vegetables, fruits and flowers post-harvest to produce prolific grey conidiophores and (macro)conidia typical of the disease. Pathogenicity:,B. cinerea produces a range of cell-wall-degrading enzymes, toxins and other low-molecular-weight compounds such as oxalic acid. New evidence suggests that the pathogen triggers the host to induce programmed cell death as an attack strategy. Resistance:, There are few examples of robust genetic host resistance, but recent work has identified quantitative trait loci in tomato that offer new approaches for stable polygenic resistance in future. Useful websites:,http://www.phi-base.org/query.php, http://www.broad.mit.edu/annotation/genome/botrytis_cinerea/Home.html, http://urgi.versailles.inra.fr/projects/Botrytis/, http://cogeme.ex.ac.uk [source] Hydrogen-bonding interaction between poly(,-caprolactone) and low-molecular-weight amino compoundsPOLYMER INTERNATIONAL, Issue 4 2001Takumi Watanabe Abstract The specific interactions between several low-molecular-weight diamino compounds and poly(,-caprolactone) (PCL) have been investigated by FT-IR. It was found that PCL and 3,3,-diaminodiphenylmethane (3,3,-DADPM) interact through strong intermolecular hydrogen bonds in the blend. Thermal and mechanical properties of PCL/3,3,-DADPM blends were investigated by DSC and tensile measurements, respectively. The glass transition temperature of the blend increases while both the melting point and the elongation-at-break of the blend decrease with the increase of 3,3,-DADPM content. Besides 3,3,-DADPM, several other low-molecular-weight compounds containing two amino groups, such as o -phenylenediamine or 1,6-diaminohexane, were also added into PCL and the corresponding blend systems were investigated by FT-IR and DSC. The effect of the chemical structure of the additives on the properties of PCL is discussed. © 2001 Society of Chemical Industry [source] Cell permeabilization by poliovirus 2B viroporin triggers bystander permeabilization in neighbouring cells through a mechanism involving gap junctionsCELLULAR MICROBIOLOGY, Issue 8 2010Vanesa Madan Summary Poliovirus 2B protein is a well-known viroporin implicated in plasma membrane permeabilization to ions and low-molecular-weight compounds during infection. Translation in mammalian cells expressing 2B protein is inhibited by hygromycin B (HB) but remains unaffected in mock cells, which are not permeable to the inhibitor. Here we describe a previously unreported bystander effect in which healthy baby hamster kidney (BHK) cells become sensitive to HB when co-cultured with a low proportion of cells expressing poliovirus 2B. Viroporins E from mouse hepatitis virus, 6K from Sindbis virus and NS4A protein from hepatitis C virus were also able to permeabilize neighbouring cells to different extents. Expression of 2B induced permeabilization of neighbouring cell lines other than BHK. We found that gap junctions are responsible mediating the observed bystander permeabilization. Gap junctional communication was confirmed in 2B-expressing co-cultures by fluorescent dye transfer. Moreover, the presence of connexin 43 was confirmed in both mock and 2B-transfected cells. Finally, inhibition of HB entry to neighbouring cells was observed with 18,-glycyrrhethinic acid, an inhibitor of gap junctions. Taken together, these findings support a mechanism involving gap junctional intercellular communication in the bystander permeabilization effect observed in healthy cells co-cultured with poliovirus 2B-expressing cells. [source] Development of a Method for the High-Throughput Quantification of Cellular ProteinsCHEMBIOCHEM, Issue 10 2009Paolo Paganetti Dr. Abstract Hunting for huntingtin: We describe a screening assay based on the inducible expression of the mutant huntingtin protein in cells and on its highly sensitive homogenous determination. Rapid, reproducible, and robust protein determination was achieved through the use of two donor,acceptor-labeled antibodies and time-resolved FRET. The assay was developed and validated for ultra-throughput screening of low-molecular-weight compounds modulating the expression of the mutant protein. The quantification of cellular proteins is essential for the study of many different biological processes. This study describes an assay for the detection of the intracellular mutant huntingtin, the causative agent of Huntington's disease, with a method that may be generally applicable to other cellular proteins. A small recombinant protein tag that is recognized by a pair of readily available, high-affinity monoclonal antibodies was designed. This tag was then added to an inducible fragment of the mutant huntingtin protein by genetic engineering. We show that it is possible to use time-resolved FRET to detect low intracellular levels of huntingtin by a simple lysis and detection procedure. This assay was then adapted into a homogeneous, miniaturized format suitable for screening in 1536-well plates. The use of time-resolved FRET also permits the assay to be multiplexed with a standard readout of cell toxicity, thus allowing the identification of conditions causing reduction of protein levels simply due to cytotoxicity. The screening results demonstrated that the assay is able to identify compounds that modulate the levels of huntingtin both positively and negatively and that represent valuable starting points for drug discovery programs. [source] Eyes Absent Proteins: Characterization of Substrate Specificity and Phosphatase Activity of Mutants Associated with Branchial, Otic and Renal AnomaliesCHEMBIOCHEM, Issue 14 2008Amna Musharraf Abstract The eyes absent (Eya) genes encode a family of proteins that combine the functions of transcriptional cofactors, signal transducers and enzymes, namely protein tyrosine phosphatases. The latter activity resides in the highly conserved C-terminal Eya domain (ED). Here, we investigated the substrate specificity of the Arabidopsis thaliana homologue (AtEya) by using low-molecular-weight compounds and synthetic phosphotyrosine (pY)-containing peptides that correspond either to phosphorylation sites in proteins or to peptides that were selected through the screening of a combinatorial peptide library. AtEya displayed modest peptide substrate specificity and was sensitive to charges adjacent to pY. In general, the presence of acidic residues on the N-terminal side of the phosphorylation site was critical for catalysis, whereas basic amino acids seemed to be preferred with respect to high-affinity binding. We also detected significant acyl phosphatase activity of AtEya; this suggests that Eya proteins might have further substrates in vivo. In addition, we analysed the phosphatase activity of a number of variants of the mouse Eya1 protein that harbours single point mutations that were associated with branchio,oto,renal syndrome (BOR), branchio,oto syndrome (BO) and ocular defects, respectively, in humans. While BOR mutations led to a significantly reduced phosphatase activity, BO mutants as well as those that are associated with ocular defects only displayed activity that was similar to wild-type levels. [source] | ||||||||||||||||