A DNA-encoded small-molecule library was prepared using yoctoReactor technology followed by binder trap enrichment to identify selective inhibitors with nanomolar potencies against p38α MAP kinase.
We optimized and validated a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of six metabolites of homocysteine metabolism: homocysteine, methionine, cysteine, S-adenosylmethionine, S-adenosylhomocysteine and betaine. The detection limits for these metabolites were in the nanomolar range, and the intra- and inter-day precisions were lower than 20% of the relative standard deviations. The method was specifically designed for the determination of the intracellular concentrations of the metabolites in cultured cells. To study the role of betaine-homocysteine S-methyltransferase (BHMT), HepG2 cells and HepG2 cells that were stably transfected with BHMT ((BHMT) HepG2) were treated with homocysteine or with a specific inhibitor of BHMT, and metabolite levels were subsequently measured. Severely compromised methyl group metabolism in the HepG2 cells, which is typical of cancer-derived cells, prevented clear evaluation of the changes caused by the external manipulations of homocysteine metabolism. However, the ease of handling these cells and the almost unlimited source of experimental material supplied by cells in permanent culture allowed us to develop a reliable methodology. The precautions concerning intracellular metabolite determinations using LC-MS/MS in cultured cells that are expressed in this work will have global validity for future metabolomics studies.
The charge carrier transport in poly[methyl(phenyl)silylene] (PMPSi) proceeds predominantly along the σ‐delocalized Si backbone with participation of interchain hopping and polaron formation. The charge carrier mobility increases with increasing electron affinity of acceptor dopands having zero dipole moments. On the other band, the hole drift mobility is influenced by the dipole moment of the dopand. The electrostatic charge‐dipole interactions cause a broadening of the energy distribution of transport states, which results in a decrease in the charge carrier mobility. An addition of organic salts leads, under the conditions of increased humidity, to an increase in electrical conductivity and capacitance. This is demonstrated on the layers PMPSi/1,5‐dimorpholino‐1,5‐diphenylpentamethinium perchlorate.
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