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101.
Janina Schmitz Norbert Furtmann Moritz Ponert Dr. Maxim Frizler Dr. Reik Löser Prof. Dr. Ulrike Bartz Prof. Dr. Jürgen Bajorath Prof. Dr. Michael Gütschow 《ChemMedChem》2015,10(8):1365-1377
Cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex class II. Cathepsin S is the major processing enzyme of the invariant chain, but cathepsin F acts in macrophages as its functional synergist which is as potent as cathepsin S in invariant chain cleavage. Dedicated low‐molecular‐weight inhibitors for cathepsin F have not yet been developed. An active site mapping with 52 dipeptide nitriles, reacting as covalent–reversible inhibitors, was performed to draw structure–activity relationships for the non‐primed binding region of human cathepsin F. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsins F, B, L, K and S. Compounds 10 (N‐(4‐phenylbenzoyl)‐leucylglycine nitrile) and 12 (N‐(4‐phenylbenzoyl)leucylmethionine nitrile) were found to be potent inhibitors of human cathepsin F, with Ki values <10 nM . With all dipeptide nitriles from our study, a 3D activity landscape was generated to visualize structure–activity relationships for this series of cathepsin F inhibitors. 相似文献
102.
103.
Dirk Jodin Christian Landschützer Norbert Hafner 《BHM Berg- und Hüttenm?nnische Monatshefte》2016,161(5):212-220
This paper introduces technical innovations in logistics engineering. Advanced simulation methods provide virtual insights in machinery behavior and support engineering development. Lab tests leading to efficiency indices help to seriously describe energy efficiency in conveying processes. 相似文献
104.
Sbastien Belot Adrien Quintard Norbert Krause Alexandre Alexakis 《Advanced Synthesis \u0026amp; Catalysis》2010,352(4):667-695
The purpose of this study is to point out the synthetic utility of a new class of Michael acceptors (nitrodienes and nitroenynes). The highly enantioselective organocatalytic Michael addition of carbonyl compounds to these functionalized nitroolefins has been carried out in the presence of (S)‐diphenylprolinol silyl ether to achieve some interesting building blocks in high selectivities. The adducts thus obtained can be easily converted by taking advantage of the corresponding unsaturated carbon‐carbon bond. In presence of the double bond, metathesis or electrophilic activation could be carried out whereas in the presence of the triple bond electrophilic activation could be conducted. We thus focused on a gold‐catalyzed cyclization of the bis‐homopropargylic alcohol to afford the corresponding substituted tetrahydrofuran. Then, we also demonstrated that organic and gold catalysts were compatible in a one‐pot process. Indeed, we developed a one‐pot enantioselective organocatalytic Michael addition to a nitroenyne followed by a gold‐catalyzed acetalization/cyclization to achieve tetrahydrofuranyl ethers in high diastereo‐ and enantioselectivities with excellent yields. 相似文献
105.
106.
Viacheslav Iablokov Krisztina Frey Olga Geszti Norbert Kruse 《Catalysis Letters》2010,134(3-4):210-216
Manganese oxides of various stoichiometry were prepared via Mn-oxalate precipitation followed by thermal decomposition in the presence of oxygen. A non-stoichiometric manganese oxide, MnO x (x = 1.61…1.67) was obtained by annealing at 633 K and demonstrated superior CO oxidation activity, i.e. full CO conversion at room temperature and below. The activity gradually decreased with time-on-stream of the reactants but could be easily recovered by heating at 633 K in the presence of oxygen. CO oxidation over MnO x in the absence of oxygen proved to be possible with reduced rates and demonstrated a Mars—van Krevelen—type mechanism to be in operation. A TEM structural analysis showed the MnO x phase to form microrods with large aspect ratio which broke up into nanocrystalline manganese oxide (MnO x ) particles with diameters below 3 nm and a BET specific surface area of 525 m2/g. Annealing at 798 K rather than 633 K produced well crystalline Mn2O3 which showed lower CO oxidation activity, i.e. 100% CO conversion at 335 K. The catalytic performance in CO oxidation of various Mn-oxides either studied in this work or elsewhere was compared on the basis of specific reaction rates. 相似文献
107.
Gundacker C Komarnicki G Jagiello P Gencikova A Dahmen N Wittmann KJ Gencik M 《The Science of the total environment》2007,385(1-3):37-47
BACKGROUND: Detoxification is an essential process in all living organisms. Humans accumulate heavy metals primarily as a result of lifestyle and environmental contamination. However, not all humans experience the estimated individual exposure. This suggests the presence of genetic regulatory mechanisms. OBJECTIVE: In order to identify genetic factors underlying the inter-individual variance in detoxification capacity for the heavy metal mercury, 192 students were investigated. We focused on the relationship between polymorphisms in glutathione-S-transferase (GST) genes and mercury concentrations in blood, urine, and hair. The correlation between blood mercury levels, GSTT1 and GSTM1 polymorphism, and gene expression of certain metallothionein subgroups (MT1, MT3) was evaluated in a further group of students (N=30). METHODS: Mercury levels in acid digested samples were measured by cold vapor AAS. Genotyping of the GSTT1 and GSTM1-gene deletion polymorphism was performed by means of PCR. Gene expression of several MT genes was analyzed in lymphocytes from fresh peripheral blood by semiquantitative RT-PCR. RESULTS: The following was noted: a) hair mercury concentrations are significantly increased in persons with the double deleted genotype (GSTT1-/- and GSTM1-/-) as compared to persons with the intact genotype, and b) MT1X expression is higher in persons with the intact genotype (GSTT1+/+ and GSTM1+/+). CONCLUSIONS: We conclude that the epistatic effect of the GSTT1 and the GSTM1 deletion polymorphism is a risk factor for increased susceptibility to mercury exposure. The relationship between MT gene expression and GST gene polymorphisms needs further investigation. If MT expression depends on GST polymorphisms it would have important implications on the overall metal detoxification capability of the human organism. 相似文献
108.
C. Bauer-Christoph Helmut Wachter Norbert Christoph Andreas Rßmann Ludwig Adam 《European Food Research and Technology》1997,204(6):445-452
Gas chromatography and the determination of natural isotope ratios are powerful analytical methods which can be used to check the authenticity of alcoholic beverages and to detect any adulteration. To check the origin and the authenticity of commercial fruit spirits, whiskies, etc., 197 samples were analysed by gas chromatography, 2H-NMR and 13C isotope mass spectrometry. The discrimination between different varieties was demonstrated by bivariate and multivariate discriminant analysis using different concentrations of volatile compounds such as methanol, butan-1-ol, 2- and 3-methyl-butanol, benzaldehyde and hexanol as well as isotopic data like (D/H)I, (D/H)II and 13C/12C isotopomers of ethanol. The results show that by using multivariate discriminant analysis it is possible to distinguish not only between different groups of spirits, e.g. those made of stone-fruit, malaceous fruit, grain and corn, but also between individual varieties, such as cherry, plum, mirabelle and apple. If the detection of highly rectified ethyl alcohol of agricultural origin and the identification of its raw materials are required, then natural isotope ratios are the only discriminant analytical parameters available. 相似文献
109.
Illa Tea Thierry Genter Norbert Naulet Marie Lummerzheim Didier Kleiber 《Journal of the science of food and agriculture》2007,87(15):2853-2859
BACKGROUND: Optimization of nitrogen (N) and sulfur (S) nutrition of wheat influences the bread‐making quality of grain. This study was conducted to determine whether the application of N and S in winter wheat at anthesis stage during two field trials could influence the absorption and distribution of N and S in grain and flour bread‐making quality RESULTS: The incorporation of 15N and 34S tracers in various plant parts (leaves, stems, spikes) was determined by isotopic ratio mass spectrometry coupled with an elemental analyser (EA‐IRMS). The effects of foliar fertilization on percentage of 15N and 34S recovery in various plant parts, grain yield, flour protein content, and dough properties were investigated after a combination of treatments: N (urea), S (micronized elemental S) and NS (both urea and micronized elemental S). Nitrogen (70–80%) and S (35–55%) were quickly assimilated during the days following application. Sixty days after application, 42–68% N and 6–12% S were recovered in the grain. When N and S fertilizers were applied simultaneously, N and S recoveries (68% and 12%), N/S ratios (11–14), flour protein content (115 g kg?1) and dough strength (310 × 10?4 J), swelling (21.8 mmH2O) and extensibility (96.4 mm) were increased. CONCLUSION: A synergistic effect between the foliar applied N and S fertilizers appears to increase N and S assimilation in grain and may improve bread‐making qualities. Copyright © 2007 Society of Chemical Industry 相似文献
110.
Microstructure of poly(isobutyl acrylate) (PiBuA) and poly(sec-butyl acrylate) (PsBuA), prepared by free radical and anionic polymerization, was investigated by 13C NMR spectroscopy. The carbonyl signal in the 100 MHz 13C NMR spectra of both homopolymers provided sufficient resolution to perform detailed analysis of distribution of configurational sequences at the pentad/heptad level. Application of Bernoulli and first order Markov statistics to determine probabilities of configurational sequences and incremental calculation to estimate chemical shifts of the individual sequences allowed for positive simulation of carbonyl signals. 相似文献