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31.
Tagging Glycoproteins with Fluorescently Labeled GDP‐Fucoses by Using α1,3‐Fucosyltransferases 下载免费PDF全文
Dr. Katrin Seelhorst Katharina Pahnke Prof. Dr. Chris Meier Prof. Dr. Ulrich Hahn 《Chembiochem : a European journal of chemical biology》2015,16(13):1919-1924
Fucose‐containing glycans mediate a variety of biological processes, but there is little information on reaction processes and mechanisms mediated by fucosyltransferases. We recently reported on fluorescently labeled GDP‐β‐L ‐fucose‐ATTO 550, which enabled monitoring of α1,3‐fucosyltransferase activity. Here we present an extension to the previously described results, based on the synthesis of a fluorescein‐isothiocyanate (FITC)‐labeled and two carboxyfluorescein‐labeled (FAM‐labeled) NDP‐β‐L ‐fucose derivatives, and applied all four compounds in labeling of different glycoproteins with the aid of four different fucosyltransferases. The labeling processes were analyzed by in‐gel fluorescence and fluorescence polarization measurements. Comparison with the ATTO‐labeled sugar revealed that the FITC‐labeled fucose was the best of these substrates, and that the bacterial enzyme HP‐FucT tolerated the fluorescent substrates better than human fucosyltransferases. 相似文献
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Aryl Bis‐Sulfonamide Inhibitors of IspF from Arabidopsis thaliana and Plasmodium falciparum 下载免费PDF全文
Jonas Thelemann Dr. Boris Illarionov Dr. Konstantin Barylyuk Dr. Julie Geist Prof. Dr. Johannes Kirchmair Dr. Petra Schneider Lucile Anthore Katharina Root Dr. Nils Trapp Prof. Dr. Adelbert Bacher Dr. Matthias Witschel Prof. Dr. Renato Zenobi Prof. Dr. Markus Fischer Prof. Dr. Gisbert Schneider Prof. Dr. François Diederich 《ChemMedChem》2015,10(12):2090-2098
2‐Methylerythritol 2,4‐cyclodiphosphate synthase (IspF) is an essential enzyme for the biosynthesis of isoprenoid precursors in plants and many human pathogens. The protein is an attractive target for the development of anti‐infectives and herbicides. Using a photometric assay, a screen of 40 000 compounds on IspF from Arabidopsis thaliana afforded symmetrical aryl bis‐sulfonamides that inhibit IspF from A. thaliana (AtIspF) and Plasmodium falciparum (PfIspF) with IC50 values in the micromolar range. The ortho‐bis‐sulfonamide structural motif is essential for inhibitory activity. The best derivatives obtained by parallel synthesis showed IC50 values of 1.4 μm against PfIspF and 240 nm against AtIspF. Substantial herbicidal activity was observed at a dose of 2 kg ha?1. Molecular modeling studies served as the basis for an in silico search targeted at the discovery of novel, non‐symmetrical sulfonamide IspF inhibitors. The designed compounds were found to exhibit inhibitory activities in the double‐digit micromolar IC50 range. 相似文献
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Human Intelligence in the Process of Semantic Content Creation 总被引:1,自引:0,他引:1
Despite significant progress over the last years the large-scale adoption of semantic technologies is still to come. One of the reasons for this state of affairs is assumed to be the lack of useful semantic content, a prerequisite for almost every IT system or application using semantics. Through its very nature, this content can not be created fully automatically, but requires, to a certain degree, human contribution. The interest of Internet users in semantics, and in particular in creating semantic content, is, however, low. This is understandable if we think of several characteristics exposed by many of the most prominent semantic technologies, and the applications thereof. One of these characteristics is the high barrier of entry imposed. Interacting with semantic technologies today requires specific skills and expertise on subjects which are not part of the mainstream IT knowledge portfolio. A second characteristic are the incentives that are largely missing in the design of most semantic applications. The benefits of using machine-understandable content are in most applications fully decoupled from the effort of creating and maintaining this content. In other words, users do not have a motivation to contribute to the process. Initiatives in the areas of the Social Semantic Web acknowledged this problem, and identified mechanisms to motivate users to dedicate more of their time and resources to participate in the semantic content creation process. Still, even if incentives are theoretically in place, available human labor is limited and must only be used for those tasks that are heavily dependent on human intervention, and cannot be reliably automated. In this article, we concentrate on this step in between. As a first contribution, we analyze the process of semantic content creation in order to identify those tasks that are inherently human-driven. When building semantic applications involving these specific tasks, one has to install incentive schemes that are likely to encourage users to perform exactly these tasks that crucially rely on manual input. As a second contribution of the article, we propose incentives or incentive-driven tools that can be used to increase user interest in semantic content creation tasks. We hope that our findings will be adopted as recommendations for establishing a fundamentally new form of design of semantic applications by the semantic technologies community. 相似文献
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Photo‐crosslinking of poly[ethene‐stat‐(methacrylic acid)] functionalised with maleimide side groups
Nadine Schmeling Katharina Hunger Gernot Engler Benjamin Breiten Patrick Rölling Alexander Mixa Claudia Staudt Karl Kleinermanns 《Polymer International》2009,58(7):720-727
BACKGROUND: Photo‐crosslinkable polymers are well known and commercially applied as photoresists. But so far they have not been applied as membrane materials for separation processes. They would offer certain advantages in membrane fabrication over conventional crosslinked polymer materials. Therefore, in this work, a poly[ethene‐stat‐(methacrylic acid)] (PEMAA) which is a potential membrane polymer for different separation problems was functionalised with photo‐crosslinkable maleimide side groups. RESULTS: It has been shown that PEMAA can be used as basic polymer material and a conversion with 3‐hydroxypropylmaleimide is possible in order to obtain a photo‐crosslinkable polymer. Investigation of the crosslinking mechanism was performed using stationary infrared and UV‐visible spectroscopy as well as nanosecond transient spectroscopy absorption measurements of a rotating film. Intense transient absorption of the maleimide‐esterified PEMAA occurs at 250 nm in the film pointing to maleimide anion formation and crosslinking via an ionic dimerisation mechanism. CONCLUSION: It is found that crosslinking reactions can be observed spectroscopically in situ using a maleimide‐functionalised PEMAA. Furthermore, experiments can be performed in the liquid phase (polymer in solution) as well as in the solid phase (polymer film) using a rotating polymer film sample. Maleimide anion formation and crosslinking via an ionic dimerisation mechanism can be investigated by variation of the polymer structure as well as the structure of the maleimide side groups. Copyright © 2009 Society of Chemical Industry 相似文献
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Picker KM 《Drug development and industrial pharmacy》2004,30(4):413-425
The aim of the study was to analyze very differently deforming materials using 3D parameter plots and consequently to gain deeper insights into the densification and deformation process described with the 3D model in order to define an ideal tableting excipient. The excipients used were dicalcium phosphate dihydrate (DCPD), sodium chloride (NaCl), microcrystalline cellulose (MCC), xylitol, mannitol, alpha-lactose monohydrate, maltose, hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC), cellulose acetate (CAC), maize starch, potato starch, pregelatinized starch, and maltodextrine. All of the materials were tableted to graded maximum relative densities (rhorel, max) using an eccentric tableting machine. The data which resulted, namely force, displacement, and time, were analyzed by the application of 3D modeling. Different particle size fractions of DCPD, CAC, and MCC were analyzed in addition. Brittle deforming materials such as DCPD exhibited a completely different 3D parameter plot, with low time plasticity, d, and low pressure plasticity, e, and a strong decrease in omega values when densification increased, in contrast to the plastically deforming MCC, which had much higher d, e, and omega values. e and omega values changed only slightly when densification increased for MCC. NaCl showed less of a decrease in omega values than DCPD did, and the d and e values were between those of MCC and DCPD. The sugar alcohols, xylitol and mannitol, behaved in a similar fashion to sodium chloride. This is also valid for the crystalline sugars, alpha-lactose monohydrate, and maltose. However, the sugars are more brittle than the sugar alcohols. The cellulose derivatives, HPMC, NaCMC, and CAC, are as plastic as MCC, however, their elasticity depends on substitution indicated by lower (more elastic) or higher (less elastic) omega values. The native starches, maize starch and potato starch, are very elastic, and pregelatinized starch and maltodextrine are less elastic and exhibited higher omega values. Deformation behavior as shown in 3D parameter plots depends on particle size for polymers such as CAC and MCC; however, it does not depend on particle size for brittle materials such as DCPD. An ideally deforming tableting excipient should exhibit high e, d, and omega values with a constant ratio of e and omega at increasing densification. 相似文献