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11.
Dr. Nan Chen Dr. Yuan Liu Yuanpei Li Prof. Dr. Chu Wang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(37):16203-16209
Protein 4′-phosphopantetheinylation is an essential post-translational modification (PTM) in prokaryotes and eukaryotes. So far, only five protein substrates of this specific PTM have been discovered in mammalian cells. These proteins are known to perform important functions, including fatty acid biosynthesis and folate metabolism, as well as β-alanine activation. To explore existing and new substrates of 4′-phosphopantetheinylation in mammalian proteomes, we designed and synthesized a series of new pantetheine analogue probes, enabling effective metabolic labelling of 4′-phosphopantetheinylated proteins in HepG2 cells. In combination with a quantitative chemical proteomic platform, we enriched and identified all the currently known 4′-phosphopantetheinylated proteins with high confidence, and unambiguously determined their exact sites of modification. More encouragingly, we discovered, using targeted chemical proteomics, a potential 4′-phosphopantetheinylation site in the protein of mitochondrial dehydrogenase/reductase SDR family member 2 (DHRS2). 相似文献
12.
Isabel V. L. Wilkinson Kelly J. Perkins Hannah Dugdale Lee Moir Aini Vuorinen Maria Chatzopoulou Sarah E. Squire Sebastian Monecke Alexander Lomow Marcus Geese Philip D. Charles Peter Burch Jonathan M. Tinsley Graham M. Wynne Stephen G. Davies Francis X. Wilson Fraydoon Rastinejad Shabaz Mohammed Kay E. Davies Angela J. Russell 《Angewandte Chemie (International ed. in English)》2020,59(6):2420-2428
Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies. 相似文献
13.
Zur Vervollkommung der strahlenchemischen Technologie für die Herstellung einiger für die Industrie wichtiger silizium-organischer Monomere und zur Durchführung von Forschungs-arbeiten auf diesem Gebiet wurde eine Pilot-Anlage unter Verwendung des Elektronenbeschleunigers EU-0,4 geschaffen, der im Physikalisch-chemischen Forschungsinstitut ?L. J. Karpow“ auf der Grundlago des Rōntgendefektoskopie-Gerātes RUP-400-5 entwickelt wurde. 相似文献
14.
J. E. Komosiński 《Isotopes in environmental and health studies》2013,49(5):199-201
Studies on the workability of precise seeders by means of labelling methods has been possible due to the solution of the following problems: labelling of seeds, radiation collimation of labelled seeds being sown, elaboration of measuring and registering systems as well as processing systems of a measuring signal. The developed method allows for precise, quick and fully objective evaluation of the studied seeders to be done under natural conditions. 相似文献
15.
16.
Hans-Detlev Gilsing Jürgen Angerer Dietrich Prescher 《Monatshefte für Chemie / Chemical Monthly》2003,134(9):1207-1213
Summary. Two ring-deuterated major metabolites of bis(2-ethylhexyl) phthalate were obtained in excellent yields by means of an improved oxidation procedure. The by-product of their interconversion by Swern oxidation is elucidated and a possible mechanism of its formation is proposed.Received February 27, 2003; accepted March 3, 2003
Published online July 28, 2003 相似文献
17.
Summary The method of iterative target transformation factor analysis (ITTFA) used in conjunction with second derivative peak finding
has shown to be a practical method for the peak deconvolution and reconstruction of HPLC chromatograms and spectra. The second
derivative method of peak finding is acceptable for resolutions above 0.5 for peaks of similar heights. Above 0.5 resolution
the labelling gives correct results where the spectra are substantially different and also when reasonably similar. Below
this value the peak labelling was still accurate where the spectra were different. Solvent effects on the spectra of the compounds
studied are small and do not hinder the peak labelling process. Thus small “local” libraries are feasible.
Presented at the 17th International Symposium on Chromatography, September 25–30, 1988. Vienna, Austria. 相似文献
18.
A new simplicial variable dimension restart algorithm is introduced to solve the nonlinear complementarity problem on the
product spaceS of unit simplices. The triangulation which underlies the algorithm differs from the triangulations ofS used thus far. Moreover, the number of rays along which the algorithm can leave the arbitrarily chosen starting point is
much larger. More precisely, there is a ray leading from the starting point to each vertex ofS. In caseS is the product ofn one-dimensional unit simplices the alogrithm is similar to the octahedral algorithm onR
n
having 2
n
rays. Also, the accuracy of an approximate solution in the terminal simplex of the algorithm is in general better than for
the other algorithms onS. Computational results will show that the number of iterations for the new algorithm is much less. The examples concern the
computation of equilibria in noncooperative games, exchange economies and trade models.
This author is financially supported by the Netherlands Organisation for the Advancement of Pure Research (ZWO), Grant 46-98.
This research is part of the VF-program “Equilibrium and Disequilibrium in Demand and Supply” which has been approved by the
Netherlands ministry of education and sciences. 相似文献
19.
设G是一个简单图,在G上当且仅当两个顶点的距离为2时增加一条边,所得的图称为G的平方,记作G2;在G上每个顶点都增加一条悬挂边所得的图称为G的冠,记作I(G).设Pn是n个顶点的路,本文给出了I(Pn2)、I(Fn)、F2n徊和I(Fn2)的序列标号. 相似文献
20.