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排序方式: 共有190条查询结果,搜索用时 156 毫秒
21.
Prof. Dr. Arun K. Ghosh Dr. Margherita Brindisi Dr. Yu-Chen Yen Emma K. Lendy Dr. Satish Kovela Emilio Leal Cárdenas Dr. Bhavanam Sekhara Reddy Dr. Kalapala Venketeswara Rao Deborah Downs Dr. Xiangping Huang Dr. Jordan Tang Prof. Dr. Andrew D. Mesecar 《ChemMedChem》2019,14(5):545-560
Herein we present the design, synthesis, and biological evaluation of potent and highly selective β-secretase 2 (memapsin 1, beta-site amyloid precursor protein cleaving enzyme 2, or BACE 2) inhibitors. BACE2 has been recognized as an exciting new target for type 2 diabetes. The X-ray structure of BACE1 bound to inhibitor 2 a {N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)propyl]amino]propyl]-5-[methyl(methylsulfonyl)amino]-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide} containing a hydroxyethylamine isostere was determined. Based on this structure, a computational docking study was performed which led to inhibitor 2 a -bound BACE2 models. These were used to optimize the potency and selectivity of inhibitors. A systematic structure–activity relationship study led to the identification of determinants of the inhibitors’ potency and selectivity toward the BACE2 enzyme. Inhibitors 2 d [N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)pentyl]amino]propyl]-N1-methyl-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide; Ki=0.031 nm , selectivity over BACE1: ≈174 000-fold] and 3 l [N1-((2S,3R)-3-hydroxy-1-phenyl-4-((3-(trifluoromethyl)benzyl)amino)butan-2-yl)-N3,5-dimethyl-N3-((R)-1-phenylethyl)isophthalamide; Ki=1.6 nm , selectivity over BACE1: >500-fold] displayed outstanding potency and selectivity. Inhibitor 3 l is nonpeptide in nature and may pave the way to the development of a new class of potent and selective BACE2 inhibitors with clinical potential. 相似文献
22.
Abhinav Anand Matteo L. Zaffalon Graziella Gariano Andrea Camellini Marina Gandini Rosaria Brescia Chiara Capitani Francesco Bruni Valerio Pinchetti Margherita Zavelani‐Rossi Francesco Meinardi Scott A. Crooker Sergio Brovelli 《Advanced functional materials》2020,30(4)
Ternary I‐III‐VI2 nanocrystals (NCs), such as CuInS2, are receiving attention as heavy‐metals‐free materials for solar cells, luminescent solar concentrators (LSCs), LEDs, and bio‐imaging. The origin of the optical properties of CuInS2 NCs are however not fully understood. A recent theoretical model suggests that their characteristic Stokes‐shifted and long‐lived luminescence arises from the structure of the valence band (VB) and predicts distinctive optical behaviours in defect‐free NCs: the quadratic dependence of the radiative decay rate and the Stokes shift on the NC radius. If confirmed, this would have crucial implications for LSCs as the solar spectral coverage ensured by low‐bandgap NCs would be accompanied by increased re‐absorption losses. Here, by studying stoichiometric CuInS2 NCs, it is revealed for the first time the spectroscopic signatures predicted for the free band‐edge exciton, thus supporting the VB‐structure model. At very low temperatures, the NCs also show dark‐state emission likely originating from enhanced electron‐hole spin interaction. The impact of the observed optical behaviours on LSCs is evaluated by Monte Carlo ray‐tracing simulations. Based on the emerging device design guidelines, optical‐grade large‐area (30×30 cm2) LSCs with optical power efficiency (OPE) as high as 6.8% are fabricated, corresponding to the highest value reported to date for large‐area devices. 相似文献
23.
Margetis George Ntoa Stavroula Antona Margherita Stephanidis Constantine 《Multimedia Tools and Applications》2019,78(10):13387-13433
Multimedia Tools and Applications - Physical paper, in its various forms (e.g. books, leaflets, catalogues), is extensively used in everyday activities, despite any advancements in digital... 相似文献
24.
James Z. Fan Nigel T. Andersen Margherita Biondi Petar Todorovi Bin Sun Olivier Ouellette Jehad Abed Laxmi K. Sagar Min‐Jae Choi Sjoerd Hoogland F. Pelayo García de Arquer Edward H. Sargent 《Advanced materials (Deerfield Beach, Fla.)》2019,31(48)
Infrared‐absorbing colloidal quantum dots (IR CQDs) are materials of interest in tandem solar cells to augment perovskite and cSi photovoltaics (PV). Today's best IR CQD solar cells rely on the use of passivation strategies based on lead iodide; however, these fail to passivate the entire surface of IR CQDs. Lead chloride passivated CQDs show improved passivation, but worse charge transport. Lead bromide passivated CQDs have higher charge mobilities, but worse passivation. Here a mixed lead‐halide (MPbX) ligand exchange is introduced that enables thorough surface passivation without compromising transport. MPbX–PbS CQDs exhibit properties that exceed the best features of single lead‐halide PbS CQDs: they show improved passivation (43 ± 5 meV vs 44 ± 4 meV in Stokes shift) together with higher charge transport (4 × 10‐2 ± 3 × 10‐3 cm2 V‐1 s‐1 vs 3 × 10‐2 ± 3 × 10‐3 cm2 V‐1 s‐1 in mobility). This translates into PV devices having a record IR open‐circuit voltage (IR Voc) of 0.46 ± 0.01 V while simultaneously having an external quantum efficiency of 81 ± 1%. They provide a 1.7× improvement in the power conversion efficiency of IR photons (>1.1 µm) relative to the single lead‐halide controls reported herein. 相似文献
25.
Stephanidis Constantine Antona Margherita 《Universal Access in the Information Society》2022,21(2):329-331
Universal Access in the Information Society - 相似文献
26.
27.
Manzo E Gavagnin M Somerville MJ Mao SC Ciavatta ML Mollo E Schupp PJ Garson MJ Guo YW Cimino G 《Journal of chemical ecology》2007,33(12):2325-2336
With the aim of establishing whether the oxidation of the tricyclic carbon skeleton of scalaradial (1) is specific to Glossodoris mollusks, the chemical investigation of specimens of Glossodoris pallida from two distinct geographical areas (China and Guam) and of Glossodoris vespa and Glossodoris averni from Eastern Australia was performed. 12-Deacetoxy-12-oxo-scalaradial (4), recently reported from another Glossodoris nudibranch, was the main metabolite of G. pallida from China, G. vespa, and G. averni. A series of scalarane compounds 3 and 5–11, including the unprecedented 12,16-deacetoxy-12-oxo-scalarafuran 5, was isolated from the mollusks. Interestingly, a population of G. pallida from Guam displayed a different scalarane pattern that was characterized by scalaradial (1), deacetyl scalaradial (2), and deoxoscalarin (3), thus confirming previous reports. The specific occurrence of 12-keto-derivatives in some nudibranchs of the genus Glossodoris is discussed. 相似文献
28.
Buxboim A Bar-Dagan M Frydman V Zbaida D Morpurgo M Bar-Ziv R 《Small (Weinheim an der Bergstrasse, Germany)》2007,3(3):500-510
We have developed a biochip platform technology suitable for controlled cell-free gene expression at the micrometer scale. A new hybrid molecule, "Daisy", was designed and synthesized to form in a single step a biocompatible lithographic interface on silicon dioxide. A protocol is described for the immobilization of linear DNA molecules thousands of base pairs long on Daisy-coated surfaces with submicrometer spatial resolution and up to high densities. On-chip protein synthesis can be obtained with a dynamic range of up to four orders of magnitude and minimal nonspecific activity. En route to on-chip artificial gene circuits, a simple two-stage gene cascade was built, in which the protein synthesized at the first location diffuses to regulate the synthesis of another protein at a second location. We demonstrate the capture of proteins from crude extract onto micrometer-scale designated traps, an important step for the formation of miniaturized self-assembled protein chips. Our biochip platform can be combined with elastomeric microfluidic devices, thereby opening possibilities for isolated and confined reaction chambers and artificial cells in which the transport of products and reagents is done by diffusion and flow. The Daisy molecule and described approach enables groups not proficient in surface chemistry to construct active biochips based on cell-free gene expression. 相似文献
29.
Margherita Stefania Sciolti Maria Antonietta Aiello Mariaenrica Frigione 《Composites Part B》2012,43(8):3239-3250
In this paper the effect of a long term immersion in water on bond durability is analyzed when FRPs (Fiber Reinforced Plastic) are externally applied to a masonry substrate. In the performed research a substrate made by natural calcareous stones, strengthened by CFRP (Carbon Fiber Reinforced Plastic) sheets has been analyzed. For a better comprehension of water effect on the adhesive bond between stone and CFRP, the same treatments were performed to the constituent materials, namely epoxy resins, CFRP sheets and stones. To this aim mechanical tests were carried out on stone, composite materials and epoxy resins before and after their immersion in water, evaluating the effects of this agent on the properties of the materials. The influence of the aging in water on the interface stone-reinforcement was analyzed in terms of bond strength, maximum bond stress, optimal bond length, slip-bond stress relationship and mode of failure. In addition the possibility of calibrating design relationships, taking into account the influence of environmental conditions is discussed. Detailed results on adhesives and composites aged in water have been reported in a previous paper while in the present work the significant decay of the mechanical properties of the stone is specifically investigated. With regard to the conditioning treatment a reduction of the bond strength has been observed (up to 26%) as well as a similar decrease of the maximum bond stress; in addition the aged specimens have shown a more fragile behavior. On the basis of the obtained results the empirical coefficient, reported in the available Italian Guidelines, to determine the FRP-masonry bond strength seems still effective when the system FRP-masonry is aged in water once the properties of the aged materials are considered in the provided relationships. 相似文献
30.