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981.
Dr. Joe Briscoe Adam Marinovic Dr. Marta Sevilla Dr. Steve Dunn Dr. Magdalena Titirici 《Angewandte Chemie (International ed. in English)》2015,54(15):4463-4468
New hybrid materials consisting of ZnO nanorods sensitized with three different biomass‐derived carbon quantum dots (CQDs) were synthesized, characterized, and used for the first time to build solid‐state nanostructured solar cells. The performance of the devices was dependent on the functional groups found on the CQDs. The highest efficiency was obtained using a layer‐by‐layer coating of two different types of CQDs. 相似文献
982.
A Potent,Selective and Cell‐Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3)
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Dr. H. Ümit Kaniskan Dr. Magdalena M. Szewczyk Dr. Zhengtian Yu Dr. Mohammad S. Eram Dr. Xiaobao Yang Keith Schmidt Dr. Xiao Luo Miao Dai Dr. Feng He Irene Zang Dr. Ying Lin Dr. Steven Kennedy Dr. Fengling Li Elena Dobrovetsky Aiping Dong Dr. David Smil Dr. Sun‐Joon Min Dr. Melissa Landon Dr. Jennifer Lin‐Jones Dr. Xi‐Ping Huang Prof. Dr. Bryan L. Roth Prof. Dr. Matthieu Schapira Dr. Peter Atadja Dr. Dalia Barsyte‐Lovejoy Prof. Dr. Cheryl H. Arrowsmith Dr. Peter J. Brown Dr. Kehao Zhao Prof. Dr. Jian Jin Prof. Dr. Masoud Vedadi 《Angewandte Chemie (International ed. in English)》2015,54(17):5166-5170
PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is essential for maturation of ribosomes, may have a role in lipogenesis, and is implicated in several diseases. A potent, selective, and cell‐active PRMT3 inhibitor would be a valuable tool for further investigating PRMT3 biology. Here we report the discovery of the first PRMT3 chemical probe, SGC707, by structure‐based optimization of the allosteric PRMT3 inhibitors we reported previously, and thorough characterization of this probe in biochemical, biophysical, and cellular assays. SGC707 is a potent PRMT3 inhibitor (IC50=31±2 nM , KD=53±2 nM ) with outstanding selectivity (selective against 31 other methyltransferases and more than 250 non‐epigenetic targets). The mechanism of action studies and crystal structure of the PRMT3‐SGC707 complex confirm the allosteric inhibition mode. Importantly, SGC707 engages PRMT3 and potently inhibits its methyltransferase activity in cells. It is also bioavailable and suitable for animal studies. This well‐characterized chemical probe is an excellent tool to further study the role of PRMT3 in health and disease. 相似文献
983.
A Functional Role for Aβ in Metal Homeostasis? N‐Truncation and High‐Affinity Copper Binding
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Mariusz Mital Nina E. Wezynfeld Tomasz Frączyk Magdalena Z. Wiloch Urszula E. Wawrzyniak Arkadiusz Bonna Carolin Tumpach Kevin J. Barnham Cathryn L. Haigh Wojciech Bal Simon C. Drew 《Angewandte Chemie (International ed. in English)》2015,54(36):10460-10464
Accumulation of the β‐amyloid (Aβ) peptide in extracellular senile plaques rich in copper and zinc is a defining pathological feature of Alzheimer′s disease (AD). The Aβ1–x (x=16/28/40/42) peptides have been the primary focus of CuII binding studies for more than 15 years; however, the N‐truncated Aβ4–42 peptide is a major Aβ isoform detected in both healthy and diseased brains, and it contains a novel N‐terminal FRH sequence. Proteins with His at the third position are known to bind CuII avidly, with conditional log K values at pH 7.4 in the range of 11.0–14.6, which is much higher than that determined for Aβ1–x peptides. By using Aβ4–16 as a model, it was demonstrated that its FRH sequence stoichiometrically binds CuII with a conditional Kd value of 3×10?14 M at pH 7.4, and that both Aβ4–16 and Aβ4–42 possess negligible redox activity. Combined with the predominance of Aβ4–42 in the brain, our results suggest a physiological role for this isoform in metal homeostasis within the central nervous system. 相似文献
984.
Comparison of mouse plasma and brain tissue homogenate sample pretreatment methods prior to high‐performance liquid chromatography for a new 1,2,4‐triazole derivative with anticonvulsant activity
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Jolanta Flieger Anna Kowalska Magdalena Pizoń Tomasz Plech Jarogniew Łuszczki 《Journal of separation science》2015,38(12):2149-2157
The focus of the study was to develop a bio‐analytical assay for a 1,2,4‐triazole derivative from plasma and brain tissue homogenate samples. The goal was to compare analytical techniques that facilitate high accuracy with simplified sample processing. In this study, commonly used standard protein precipitation and solid‐phase extraction methods utilizing C18 and cartridges of Hybrid technology were compared in terms of their ability for sample pretreatment and removal of biological matrices before high‐performance liquid chromatography quantification. Fast classical reversed‐phase chromatography on a C18 column paired with selective sample preparation using Hybrid solid‐phase extraction technology resulted in the most precise bio‐analytical determination of the hydrophobic 1,2,4‐triazole derivative in both biological samples studied. The obtained recovery values were above 95% with the coefficient of variation lower than 5%. 相似文献
985.
Magdalena Maecka Agnieszka Rybarczyk‐Pirek Tomasz A. Olszak Katarzyna Malinowska Justyn Ochocki 《Acta Crystallographica. Section C, Structural Chemistry》2001,57(5):513-514
The X‐ray structure analysis of [Ni(C5H8N2)4(H2O)2]Cl2 was undertaken to elucidate the geometry around the Ni2+ ion. The molecule lies on a twofold axis which runs through the O—Ni—O atoms. The geometry around the Ni2+ ion is best described as slightly distorted tetragonal bipyramidal. 相似文献
986.
Getting access to the effective diffusion coefficient is a key point to provide realistic predictions of migration of radionuclides from radioactive waste repository in deep argillaceous geological formations. In the present work, the effective diffusion coefficient was computed inside an argillite micro-fracture as a function of its saturation level. The micrometric fracture geometry was extracted from the X-ray \(\mu \)-tomography image (\(0.7\,\upmu \mathrm{m}\) voxel resolution) of an Opalinus clay sample. It was collected in the host rock excavated damaged zone surrounding a borehole in the Mont Terri laboratory. The computations were performed using two two-relaxation-time lattice Boltzmann models. The first one, a phase separation model, was used to extract the connected liquid phase inside the fracture for given saturations. The second, a diffusion model, was used to compute non-reactive tracer diffusion in the connected liquid phase of the fracture and to calculate the effective diffusion coefficient for the associated saturations. The dependence of the effective diffusion coefficient on saturation was found to be quasi-linear and to qualitatively match the Maxwell expression for saturations lower than 0.8. 相似文献
987.
Łukasz Piskorski Magdalena Marciniak Jarosław Walczak 《Optical and Quantum Electronics》2017,49(5):199
We present the simulation results of threshold operation of mid-infrared GaSb-based vertical-cavity surface-emitting lasers (VCSELs) obtained with the use of comprehensive fully self-consistent optical-electrical-thermal-recombination numerical model. The results show that by a proper design of VCSEL structure and composition of the active region it is theoretically possible to achieve room-temperature (RT) threshold operation for wavelength of 2.8 μm which is about 0.2 μm longer than those reported so far in the literature for III-V VCSELs with type-I quantum wells. Calculated values of the RT threshold current were equal to 2.5 and 4.0 mA for tunnel-junction diameters of 2 and 4 μm, respectively. 相似文献
988.
Corentin Bon Yang Si Melanie Pernak Magdalena Barbachowska Eva Levi-Acobas Veronique Cadet Daniel Corinne Jallet Dusan Ruzic Nemanja Djokovic Teodora Djiki Katarina Nikolic Ludovic Halby Paola B. Arimondo 《Molecules (Basel, Switzerland)》2021,26(17)
Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect. 相似文献
989.
Thierry Hamaide Magdalena Pantiru Hatem Fessi Paul Boullanger 《Macromolecular rapid communications》2001,22(9):659-663
Functionalised polycaprolactones have been obtained by anionic coordinated ring‐opening polymerisation with Al(OiPr)3 as the initiator in the presence of monosaccharides as transfer agents. 1H and 13C NMR spectroscopy, as well as MALDI‐TOF mass spectrometry clearly show the functionalisation of the polycaprolactone chains. Protected monosaccharides bearing primary hydroxyl groups are suited best to get well‐controlled polymer chains. Polycaprolactones functionalised with galactopyranose end groups have been used for the preparation of nanoparticles according to the emulsification‐diffusion procedure. Nanospheres and nanocapsules with diameters around 0.50 μm could be obtained. 相似文献
990.
Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women’s osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RANK/RANKL signaling provides the opportunity to design novel therapeutic agents to inhibit bone loss, based on the anti-RANKL treatment and inhibition of its interaction with the RANK receptor. The new generation of both anti- and mesoprogestins that inhibit the NF-κB-cyclin D1 axis and blocks the binding of RANKL to RANK can be considered as a potential source of new RANK receptor ligands with anti-RANKL function, which may provide a new perspective into osteoporosis treatment itself as well as limit the osteoporosis rise during breast cancer metastasis to the bone. 相似文献