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51.
Quentin Coquerel Claire Legendre Jacinthe Frangieh Stephan De Waard Jrme Montnach Leos Cmarko Joseph Khoury Charifat Said Hassane Dimitri Brard Benjamin Siegler Ziad Fajloun Harold De Pomyers Kamel Mabrouk Norbert Weiss Daniel Henrion Pascal Richomme Csar Mattei Michel De Waard Anne-Marie Le Ray Christian Legros 《Molecules (Basel, Switzerland)》2022,27(13)
Voltage-gated Na+ (NaV) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel NaV channel ligands. With the objective of discovering new blockers of NaV channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of NaV channels with batrachotoxin (BTX) in GH3b6 cells. This led to the selection of five IA: liriodenine, oxostephanine, thalmiculine, protopine, and bebeerine, inhibiting the BTX-induced VSP signal with micromolar IC50. These five alkaloids were then assayed using the Na+ fluorescent probe ANG-2 and the patch-clamp technique. Only oxostephanine and liriodenine were able to inhibit the BTX-induced ANG-2 signal in HEK293-hNaV1.3 cells. Indeed, liriodenine and oxostephanine decreased the effects of BTX on Na+ currents elicited by the hNaV1.3 channel, suggesting that conformation change induced by BTX binding could induce a bias in fluorescent assays. However, among the five IA selected in the VSP assay, only bebeerine exhibited strong inhibitory effects against Na+ currents elicited by the hNav1.2 and hNav1.6 channels, with IC50 values below 10 µM. So far, bebeerine is the first BBIQ to have been reported to block NaV channels, with promising therapeutical applications. 相似文献
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Kerstin Zab Detlev Joachimi Eva Novotna Siegmar Diele Carsten Tschierske 《Liquid crystals》2013,40(4):631-637
Abstract Various trimeric co-oligomers combining 2-phenyl-1,3,4-thiadiazole mesogenic moieties with a biphenyl mesogenic moiety were synthesized and their mesomorphic behaviour investigated by polarizing microscopy, calorimetry and X-ray scattering. Such co-oligomeric structures provide an opportunity to combine different mesogenic units. Thus readily accessible homochiral biphenyl mesogenic units were connected with thiadiazole mesogenic units leading to an oligomeric liquid crystal material with ferroelectric properties. 相似文献
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Rongji Liu Kecheng Cao Adam H. Clark Peilong Lu Montaha Anjass Johannes Biskupek Ute Kaiser Guangjin Zhang Carsten Streb 《Chemical science》2020,11(4):1043
The top-down fabrication of catalytically active molecular metal oxide anions, or polyoxometalates, is virtually unexplored, although these materials offer unique possibilities, for catalysis, energy conversion and storage. Here, we report a novel top-down route, which enables the scalable synthesis and deposition of sub-nanometer molybdenum-oxo clusters on electrically conductive mesoporous carbon. The new approach uses a unique redox-cycling process to convert crystalline MoIVO2 particles into sub-nanometer molecular molybdenum-oxo clusters with a nuclearity of ∼1–20. The resulting molybdenum-oxo cluster/carbon composite shows outstanding, stable electrocatalytic performance for the oxygen reduction reaction with catalyst characteristics comparable to those of commercial Pt/C. This new material design could give access to a new class of highly reactive polyoxometalate-like metal oxo clusters as high-performance, earth abundant (electro-)catalysts.The top-down synthesis and deposition of polyoxometalate-like clusters on porous carbon is reported together with the high electrocatalytic oxygen reduction reactivity of the composite. 相似文献
57.
We present the design and experimental characterization of a monolithic optical time-division multiplexer (MUX) for 160 Gbit/s operation based on periodically poled lithium niobate (PPLN) waveguides. Its key figures of merit agree well with theoretical predictions and meet or exceed those of a previously demonstrated PPLN-planar-light-wave-circuit hybrid MUX. The monolithic design has a simpler layout and higher efficiency while keeping the cross talk low. 相似文献
58.
Victor U. Weiss Natalia Denderz Günter Allmaier Martina Marchetti-Deschmann 《Electrophoresis》2021,42(11):1202-1208
Gas-phase electrophoresis yields size distributions of polydisperse, aerosolized analytes based on electrophoretic principles. Nanometer-sized, surface-dry, single-charged particles are separated in a high laminar sheath flow of particle-free air and an orthogonal tunable electric field. Additionally, nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analyzer (nES GEMMA) data are particle-number based. Therefore, small particles can be detected next to larger ones without a bias, for example, native proteins next to their aggregates. Analyte transition from the liquid to the gas phase is a method inherent prerequisite. In this context, nonvolatile sample buffers influence results. In the worst case, the (bio-)nanoparticle signal is lost due to an increased baseline and unspecific clustering of nonvolatile components. We present a novel online hyphenation of liquid chromatography and gas-phase electrophoresis, coupling a size-exclusion chromatography (SEC) column to an advanced nES GEMMA. Via this novel approach, it is possible to (i) separate analyte multimers already present in liquid phase from aggregates formed during the nES process, (ii) differentiate liquid phase and spray-induced multimers, and (iii) to remove nonvolatile buffer components online before SEC–nES GEMMA analysis. Due to these findings, SEC–nES GEMMA has the high potential to help to understand aggregation processes in biological buffers adding the benefit of actual size determination for noncovalent assemblies formed in solution. As detection and characterization of protein aggregation in large-scale pharmaceutical production or sizing of noncovalently bound proteins are findings directly related to technologically and biologically relevant situations, we proposed the presented method to be a valuable addition to LC-MS approaches. 相似文献
59.
Dr. Xinghai Ning Dr. Wonewoo Seo Dr. Seungjun Lee Dr. Kiyoko Takemiya Dr. Mohammad Rafi Dr. Xuli Feng Dr. Daiana Weiss Dr. Xiaojian Wang Larry Williams Vernon M. Camp Malveaux Eugene Prof. W. Robert Taylor Prof. Mark Goodman Prof. Niren Murthy 《Angewandte Chemie (International ed. in English)》2014,53(51):14096-14101
A positron emission tomography (PET) tracer composed of 18F‐labeled maltohexaose (MH18F) can image bacteria in vivo with a sensitivity and specificity that are orders of magnitude higher than those of fluorodeoxyglucose (18FDG). MH18F can detect early‐stage infections composed of as few as 105 E. coli colony‐forming units (CFUs), and can identify drug resistance in bacteria in vivo. MH18F has the potential to improve the diagnosis of bacterial infections given its unique combination of high specificity and sensitivity for bacteria. 相似文献
60.
Christian Schumacher Dr. José G. Hernández Prof. Dr. Carsten Bolm 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(38):16499-16502
The formation and regeneration of active CuI species is a fundamental mechanistic step in copper-catalyzed atom transfer radical cyclizations (ATRC). Typically, the presence of the catalytically active CuI species in the reaction mixture is secured by using high CuI catalyst loadings or the addition of complementary reducing agents. In this study it is demonstrated how the piezoelectric properties of barium titanate (BaTiO3) can be harnessed by mechanical ball milling to induce electrical polarization in the strained piezomaterial. This strategy enables the conversion of mechanical energy into electrical energy, leading to the reduction of a CuII precatalyst into the active CuI species in copper-catalyzed mechanochemical solvent-free ATRC reactions. 相似文献