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51.
Back Cover: [3H]UR‐DE257: Development of a Tritium‐Labeled Squaramide‐Type Selective Histamine H2 Receptor Antagonist (ChemMedChem 1/2015) 下载免费PDF全文
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53.
Sabrina Reich Dr. Hans Wolfgang Hoeffken Dr. Bettina Rosche Dr. Bettina M. Nestl Prof. Dr. Bernhard Hauer 《Chembiochem : a European journal of chemical biology》2012,13(16):2400-2407
The crystal structure of the “ene” nicotinamide‐dependent cyclohexenone reductase (NCR) from Zymomonas mobilis (PDB ID: 4A3U) has been determined in complex with acetate ion, FMN, and nicotinamide, to a resolution of 1.95 Å. To study the activity and enantioselectivity of this enzyme in the bioreduction of activated α,β‐unsaturated alkenes, the rational design methods site‐ and loop‐directed mutagenesis were applied. Based on a multiple sequence alignment of various members of the Old Yellow Enzyme family, eight single‐residue variants were generated and investigated in asymmetric bioreduction. Furthermore, a structural alignment of various ene reductases predicted four surface loop regions that are located near the entrance of the active site. Four NCR loop variants, derived from loop‐swapping experiments with OYE1 from Saccharomyces pastorianus, were analysed for bioreduction. The three enzyme variants, P245Q, D337Y and F314Y, displayed increased activity compared to wild‐type NCR towards the set of substrates tested. The active‐site mutation Y177A demonstrated a clear influence on the enantioselectivity. The loop‐swapping variants retained reduction efficiency, but demonstrated decreased enzyme activity compared with the wild‐type NCR ene reductase enzyme. 相似文献
54.
Leonhard M. Kick Dr. Sabrina Harteis Dr. Maximilian F. Koch Dr. Sabine Schneider 《Chembiochem : a European journal of chemical biology》2017,18(22):2242-2246
Inteins carry out protein-splicing reactions, which are used in protein chemistry, protein engineering and biotechnological applications. Rearrangement of the order of the domains in split-inteins results in head-to-tail cyclisation of the target sequence, which can be used for genetic encoding and expression of libraries of cyclic peptides (CPs). The efficiency of the splicing reaction depends on the target sequence. Here we used mass spectrometry to assess in vivo cyclic peptide formation from different hexameric target sequences by the DnaE split-inteins from Synechocystis sp. and Nostoc punctiforme, revealing a strong impact of the target sequence and of the intein on the intracellular peptide concentration. Furthermore, we determined the crystal structures of their pre-splicing complexes, which allowed us to identify F-block Asp17 as crucial for the DnaE-mediated splicing reaction. 相似文献
55.
Ivie L. Conlon Dr. Brandon Drennen Dr. Maryanna E. Lanning Samuel Hughes Rebecca Rothhaas Dr. Paul T. Wilder Dr. Alexander D. MacKerell Jr. Dr. Steven Fletcher 《ChemMedChem》2020,15(18):1691-1698
Protein–protein interactions (PPIs), many of which are dominated by α-helical recognition domains, play key roles in many essential cellular processes, and the dysregulation of these interactions can cause detrimental effects. For instance, aberrant PPIs involving the Bcl-2 protein family can lead to several diseases including cancer, neurodegenerative diseases, and diabetes. Interactions between Bcl-2 pro-life proteins, such as Mcl-1, and pro-death proteins, such as Bim, regulate the intrinsic pathway of apoptosis. p53, a tumor-suppressor protein, also has a pivotal role in apoptosis and is negatively regulated by its E3 ubiquitin ligase HDM2. Both Mcl-1 and HDM2 are upregulated in numerous cancers, and, interestingly, there is crosstalk between both protein pathways. Recently, synergy has been observed between Mcl-1 and HDM2 inhibitors. Towards the development of new anticancer drugs, we herein describe a polypharmacology approach for the dual inhibition of Mcl-1 and HDM2 by employing three densely functionalized isoxazoles, pyrazoles, and thiazoles as mimetics of key α-helical domains of their partner proteins. 相似文献
56.
Jun.-Prof. Dr. Sabrina Hedrich Mareike Fritze Prof. Dr. Axel Schippers 《化学,工程师,技术》2023,95(12):1897-1908
Biohydrometallurgy as a section of hydrometallurgy uses specific metabolic capabilities of microorganisms for metal extraction. Biomining is the application of bioleaching for metal extraction from sulfide ores. For recycling, i.e., metal extraction from waste and industrial residues, there are no biohydrometallurgical technologies yet, but promising laboratory studies on metal extraction from solids. In this review article, these are summarized, and perspectives are shown. 相似文献
57.
Dr. Rebecca E. Moore Sabrina K. Spicer Julie A. Talbert Dr. Shannon D. Manning Dr. Steven D. Townsend Dr. Jennifer A. Gaddy 《Chembiochem : a European journal of chemical biology》2023,24(6):e202200643
Group B Streptococcus (GBS) is an encapsulated Gram-positive bacterial pathogen that causes severe perinatal infections. Human milk oligosaccharides (HMOs) are short-chain sugars that have recently been shown to possess antimicrobial and anti-biofilm activity against a variety of bacterial pathogens, including GBS. We have expanded these studies to demonstrate that HMOs can inhibit and dismantle biofilm in both invasive and colonizing strains of GBS. A cohort of 30 diverse strains of GBS were analyzed for susceptibility to HMO-dependent biofilm inhibition or destruction. HMOs were significantly effective at inhibiting biofilm in capsular-type- and sequence-type-specific fashion, with significant efficacy in CpsIb, CpsII, CpsIII, CpsV, and CpsVI strains as well as ST-1, ST-12, ST-19, and ST-23 strains. Interestingly, CpsIa as well as ST-7 and ST-17 were not susceptible to the anti-biofilm activity of HMOs, underscoring the strain-specific effects of these important antimicrobial molecules against the perinatal pathogen Streptococcus agalactiae. 相似文献
58.
Reginaldo Muccillo Sabrina G. M. Carvalho Rafael L. Denaldi Eliana N. S. Muccillo 《International Journal of Applied Ceramic Technology》2023,20(2):951-958
Molten Na2CO3–K2CO3 (NKC, 56–44 mol%) eutectic compositions were vacuum-impregnated, at the eutectic temperature, into two porous ZrO2:8.6 mol% MgO (magnesium-partially stabilized zirconia, MgPSZ) and ZrO2:8 mol% Y2O2 (yttria-fully stabilized zirconia, 8YSZ) ceramics. Thermogravimetric analyses were performed in mixtures of that composition with MgPSZ and 8YSZ ceramic powders. Before impregnation, porosity was achieved in the two compounds by addition and thermal removal of 30 vol.% NKC. To ascertain the carbonates had filled up through the ceramic body, both sides of the parallel and fracture surfaces of the disk-shaped impregnated compositions were observed in a scanning electron microscope and analyzed by energy-dispersive X-ray spectroscopy. The electrical conductivity of the two ceramics, before and after impregnation, was evaluated by electrochemical impedance spectroscopy in the 5 Hz–13 MHz frequency range from approximately 530 to 740°C. The permeation of the carbonate ions through the membranes via the eutectic composition was assessed by the threshold temperatures of the onset of the carbonate ion percolation. The objectives were to prepare dual-phase membranes for the separation of carbon dioxide and for the development of carbon dioxide sensors. 相似文献
59.
Diffusion coefficients D of H 2 , He, O 2 , N 2 , and CO 2 in different rubbery amorphous polymeric matrices were estimated by atomistic molecular dynamics simulations at 298 K using the Einstein relationship, and compared with the relevant experimental values, where available. The simulated diffusion coefficients D of all the gases in all polymers considered almost regularly decreased with increasing molecular gas volumes and increasing polymer glass transition temperature. Further, solubility coefficients and heats of solution were obtained for all gases from Grand Canonical Monte Carlo simulations, which were also used to calculate sorption isotherms. In general, there is a good agreement between experimental and simulated values of diffusion and solubility coefficients for all gases considered. 相似文献
60.
Alessandro Martucci Sabrina Sartori Alessandro Muffato Lidia Armelao Elisabetta Di Bartolomeo Enrico Traversa Massimo Guglielmi 《Journal of the American Ceramic Society》2003,86(11):1965-1968
Na2 O· x Al2 O3 ( x = 9, 11)films have been obtained by sol–gel method. Crystallization processes during heat treatments have been investigated by X–ray diffraction analysis. A metastable phase with the mullite structure, λ–Na2 O· x Al2 O3 , has been observed starting from 800°C. Films remained stable after a heat treatment at 1000°C for 250 h. Impedance spectroscopy measurements showed that the films of λ-Na2 O· x Al2 O3 possess a large three–dimensional ionic conductivity at 400°C. 相似文献