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51.
François Bilodeau Murray D. Bailey Punit K. Bhardwaj Josée Bordeleau Pat Forgione Michel Garneau Elise Ghiro Vida Gorys Ted Halmos Eric S. Jolicoeur Mélissa Leblanc Christopher T. Lemke Julie Naud Jeff O’Meara Peter W. White Montse Llinàs-Brunet 《Bioorganic & medicinal chemistry letters》2013,23(14):4267-4271
In this report we describe the synthesis and evaluation of diverse 4-arylproline analogs as HCV NS3 protease inhibitors. Introduction of this novel P2 moiety opened up new SAR and, in combination with a synthetic approach providing a versatile handle, allowed for efficient exploitation of this novel series of NS3 protease inhibitors. Multiple structural modifications of the aryl group at the 4-proline, guided by structural analysis, led to the identification of analogs which were very potent in both enzymatic and cell based assays. The impact of this systematic SAR on different drug properties is reported. 相似文献
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Terry A. Gray Euan Murray Matthew W. Nowicki Lucy Remnant Alexander Scherl Petr Muller Borek Vojtesek Ted R. Hupp 《Protein science : a publication of the Protein Society》2013,22(9):1266-1278
Many regulatory proteins are homo‐oligomeric and designing assays that measure self‐assembly will provide novel approaches to study protein allostery and screen for novel small molecule modulators of protein interactions. We present an assay to begin to define the biochemical determinants that regulate dimerization of the cancer‐associated oncoprotein AGR2. A two site‐sandwich microtiter assay (2SMTA) was designed using a DyLight800‐labeled monoclonal antibody that binds to an epitope in AGR2 to screen for synthetic self‐peptides that might regulate dimer stability. Peptides derived from the intrinsically disordered N‐terminal region of AGR2 increase in trans oligomer stability as defined using the 2SMTA assay. A DSS‐crosslinking assay that traps the AGR2 dimer through K95‐K95 adducts confirmed that Δ45‐AGR2 was a more stable dimer using denaturing gel electrophoresis. A titration of wt‐AGR2, Δ45‐AGR2 (more stable dimer), and monomeric AGR2E60A revealed that Δ45‐AGR2 was more active in binding to Reptin than either wt‐AGR2 or the AGR2E60A mutant. Our data have defined a functional role for the AGR2 dimer in the binding to its most well characterized interacting protein, Reptin. The ability to regulate AGR2 oligomerization in trans opens the possibility for developing small molecules that regulate its' biochemical activity as potential cancer therapeutics. The data also highlight the utility of this oligomerization assay to screen chemical libraries for ligands that could regulate AGR2 dimer stability and its' oncogenic potential. 相似文献
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Ákos Szekrényes SungAe Suhr Park Marcia Santos Clarence Lew Aled Jones Ted Haxo 《MABS-AUSTIN》2016,8(1):56-64
An international team that included 20 independent laboratories from biopharmaceutical companies, universities, analytical contract laboratories and national authorities in the United States, Europe and Asia was formed to evaluate the reproducibility of sample preparation and analysis of N-glycans using capillary electrophoresis of 8-aminopyrene-1,3,6-trisulfonic acid (APTS)-labeled glycans with laser induced fluorescence (CE-LIF) detection (16 sites) and ultra high-performance liquid chromatography (UHPLC, 12 sites; results to be reported in a subsequent publication). All participants used the same lot of chemicals, samples, reagents, and columns/capillaries to run their assays. Migration time, peak area and peak area percent values were determined for all peaks with >0.1% peak area. Our results demonstrated low variability and high reproducibility, both, within any given site as well across all sites, which indicates that a standard N-glycan analysis platform appropriate for general use (clone selection, process development, lot release, etc.) within the industry can be established. 相似文献
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Powdery mildew suppresses herbivore‐induced plant volatiles and interferes with parasitoid attraction in Brassica rapa 下载免费PDF全文
The co‐occurrence of different antagonists on a plant can greatly affect infochemicals with ecological consequences for higher trophic levels. Here we investigated how the presence of a plant pathogen, the powdery mildew Erysiphe cruciferarum, on Brassica rapa affects (1) plant volatiles emitted in response to damage by a specialist herbivore, Pieris brassicae; (2) the attraction of the parasitic wasp Cotesia glomerata and (3) the performance of P. brassicae and C. glomerata. Plant volatiles were significantly induced by herbivory in both healthy and mildew‐infected plants, but were quantitatively 41% lower for mildew‐infected plants compared to healthy plants. Parasitoids strongly preferred Pieris‐infested plants to dually‐infested (Pieris + mildew) plants, and preferred dually infested plants over only mildew‐infected plants. The performance of P. brassicae was unaffected by powdery mildew, but C. glomerata cocoon mass was reduced when parasitized caterpillars developed on mildew‐infected plants. Thus, avoidance of mildew‐infested plants may be adaptive for C. glomerata parasitoids, whereas P. brassicae caterpillars may suffer less parasitism on mildew‐infected plants in nature. From a pest management standpoint, the concurrent presence of multiple plant antagonists can affect the efficiency of specific natural enemies, which may in turn have a negative impact on the regulation of pest populations. 相似文献
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Large-scale parasite quantification is required for improving our understanding of the epidemiology and genetics of host-parasite interactions. We describe a protocol that uses a low-density salt solution for flotation and centrifugation of nematode eggs. Subsequently, sucrose flotation and precipitation are used to obtain clear egg preparations. Most traditional quantification protocols such as the McMaster technique are unsuited for the standardized processing of large numbers of samples and the analysis of large amounts of feces per sample. Consequently, they are suited only for small-scale surveys. Our protocol, which can be used to analyze up to 6 g of feces, results in clear egg preparations that are concentrated in wells of a microtiter plate and that are suited for digital recording and automated counting. Starting from a fecal suspension in the first flotation solution to a digital recording requires approximately 40 min per 24 samples. 相似文献
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The large variety of clustering algorithms and their variants can be daunting to researchers wishing to explore patterns within their microarray datasets. Furthermore, each clustering method has distinct biases in finding patterns within the data, and clusterings may not be reproducible across different algorithms. A consensus approach utilizing multiple algorithms can show where the various methods agree and expose robust patterns within the data. In this paper, we present a software package - Consense, written for R/Bioconductor - that utilizes such an approach to explore microarray datasets. Consense produces clustering results for each of the clustering methods and produces a report of metrics comparing the individual clusterings. A feature of Consense is identification of genes that cluster consistently with an index gene across methods. Utilizing simulated microarray data, sensitivity of the metrics to the biases of the different clustering algorithms is explored. The framework is easily extensible, allowing this tool to be used by other functional genomic data types, as well as other high-throughput OMICS data types generated from metabolomic and proteomic experiments. It also provides a flexible environment to benchmark new clustering algorithms. Consense is currently available as an installable R/Bioconductor package (http://www.ohsucancer.com/isrdev/consense/). 相似文献
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Goldberg E. Grace Raab Ted K. Desalles Paul Briggs Amy A. Dunbar Robert B. Millero Frank J. Woosley Ryan J. Young Hillary S. Micheli Fiorenza Mccauley Douglas J. 《Coral reefs (Online)》2019,38(2):347-357
Coral Reefs - Bolbometopon muricatum are ecologically unique mega-consumers in coral reef ecosystems. They primarily divide their dietary intake between living scleractinian corals and coral rock,... 相似文献
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