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1.
[reaction: see text] A practical synthesis of the potent class I alpha-mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily available starting material L-ascorbic acid (15) is described. The protected amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisopropylidenedioxyhexanol, 11) served as a key intermediate from which several N-1 substituted kifunensine analogues (including N-methyl, N-cyclohexyl, and N-bis(hydroxymethyl)methyl) and 2-desoxakifunensine analogues (including N-H and N-methyl) were prepared and screened for inhibition of human endoplasmic reticulum alpha-mannosidase I (ER Man I) and mouse Golgi alpha-mannosidase IA (Golgi Man IA). In addition, several pseudodisaccharide kifunensine analogues in which a mannose residue was tethered to N-1 of kifunensine via a two-, three-, or four-carbon linker and an affinity-bound kifunensine analogue were also prepared and evaluated for biological activity. While the synthesized N-1 kifunesine analogues were found to be less potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the bis(hydroxymethyl)methylkifunensine analogue 6 was shown to selectively inhibit ER Man I over Golgi Man IA. 相似文献
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Lexicographic or first choice constructions of geometric objects sometimes lead to amazingly good results. Usually it is difficult to determine the precise identity of the resulting geometries. Here we find infinitely many cases where the identification actually can be accomplished. 相似文献
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Justyna Stefanowicz-Hajduk Anna Hering Magdalena Gucwa Katarzyna Sztormowska-Achranowicz Mariusz Kowalczyk Agata Soluch J. Renata Ochocka 《Molecules (Basel, Switzerland)》2022,27(7)
Kalanchoe species are succulents with anti-inflammatory, antioxidant, and analgesic properties, as well as cytotoxic activity. One of the most popular species cultivated in Europe is Kalanchoe daigremontiana Raym.-Hamet and H. Perrier. In our study, we analyzed the phytochemical composition of K. daigremontiana water extract using UHPLC-QTOF-MS and estimated the cytotoxic activity of the extract on human ovarian cancer SKOV-3 cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry, luminometric, and fluorescent microscopy techniques. The expression levels of 92 genes associated with cell death were estimated via real-time PCR. The antioxidant activity was assessed via flow cytometry on human keratinocyte HaCaT cell line. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical and FRAP (ferric-reducing antioxidant power) assays were also applied. We identified twenty bufadienolide compounds in the water extract and quantified eleven. Bersaldegenin-1,3,5-orthoacetate and bryophyllin A were present in the highest amounts (757.4 ± 18.7 and 573.5 ± 27.2 ng/mg dry weight, respectively). The extract showed significant antiproliferative and cytotoxic activity, induced depolarization of the mitochondrial membrane, and significantly arrested cell cycle in the S and G2/M phases of SKOV-3 cells. Caspases-3, 7, 8, and 9 were not activated during the treatment, which indicated non-apoptotic cell death triggered by the extract. Additionally, the extract increased the level of oxidative stress in the cancer cell line. In keratinocytes treated with menadione, the extract moderately reduced the level of oxidative stress. This antioxidant activity was confirmed by the DPPH and FRAP assays, where the obtained IC50 values were 1750 ± 140 and 1271.82 ± 53.25 μg/mL, respectively. The real-time PCR analysis revealed that the extract may induce cell death via TNF receptor (tumor necrosis factor receptor) superfamily members 6 and 10. 相似文献
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提出了强拟Armendariz环的概念,给出了强Armendariz环和强拟Armendariz环上的一些结果. 相似文献
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F. Müller G. von Basum A. Popp D. Halmer P. Hering M. Mürtz F. Kühnemann S. Schiller 《Applied physics. B, Lasers and optics》2005,80(3):307-313
We present a frequency stability and linewidth analysis of two different setups of continuous-wave pump and signal-resonant optical parametric oscillators (pump resonant, singly resonant OPO, PR-SRO). Both designs, a common-cavity and a dual-cavity version, utilize a frequency-stable and narrow-linewidth pump laser and are stabilized without using an external reference. A long-term frequency stability better than ±30 MHz is reached over more than 30 minutes for both designs. The frequency jitter on a one-second time-scale is 56 kHz for the common-cavity PR-SRO and about 10 MHz for the dual-cavity PR-SRO. The short-term linewidths were measured using an external high-finesse cavity and are (9±2)kHz and (6±1)kHz in 20 s, respectively. To our knowledge, these are the lowest values demonstrated so far for a widely continuously wavelength-tunable all-solid-state laser source. PACS 42.65.Yj; 42.72.Ai; 42.62.Fi 相似文献
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Halmer D von Basum G Horstjann M Hering P Mürtz M 《Isotopes in environmental and health studies》2005,41(4):303-311
We present a ring-down absorption spectrometer based on a continuous-wave CO laser in the mid-infrared spectral region near lambda = 5 microm. Using a linear ring-down cavity (length: 0.5 m) with high reflective mirrors (R = 99.988 %), we observed a noise-equivalent absorption coefficient of 3 x 10(-10) cm(-1)Hz(-1/2). This corresponds to a noise-equivalent concentration of 800 parts per trillion (ppt) for (14)NO and 40 ppt for (15)NO in 1 s averaging time. We achieve a time resolution of 1 s which allows time resolved simultaneous detection of the two N isotopes. The delta(15)N value was obtained with a precision of +/-1.2 per thousand in a sample with a NO fraction of 11 ppm. The simultaneous detection enables the use of (15)NO as a tracer molecule for endogenous biomedical processes. 相似文献
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Adamová D Agakichiev G Appelshäuser H Belaga V Braun-Munzinger P Castillo A Cherlin A Damjanović S Dietel T Dietrich L Drees A Esumi SI Filimonov K Fomenko K Fraenkel Z Garabatos C Glässel P Hering G Holeczek J Kushpil V Lenkeit B Ludolphs W Maas A Marín A Milosević J Milov A Miśkowiec D Panebrattsev Y Petchenova O Petrácek V Pfeiffer A Rak J Ravinovich I Rehak P Sako H Schmitz W Schukraft J Sedykh S Shimansky S Slívová J Specht HJ Stachel J Sumbera M Tilsner H Tserruya I Wessels JP Wienold T 《Physical review letters》2003,90(2):022301
Based on an evaluation of data on pion interferometry and on particle yields at midrapidity, we propose a universal condition for thermal freeze-out of pions in heavy-ion collisions. We show that freeze-out occurs when the mean free path of pions lambda(f) reaches a value of about 1 fm, which is much smaller than the spatial extent of the system at freeze-out. This critical mean free path is independent of the centrality of the collision and beam energy from the Alternating Gradient Synchrotron to the Relativistic Heavy Ion Collider. 相似文献