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排序方式: 共有807条查询结果,搜索用时 640 毫秒
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Heidler P Zohrabi-Kalantari V Calmels T Capet M Berrebi-Bertrand I Schwartz JC Stark H Link A 《Bioorganic & medicinal chemistry》2005,13(6):2009-2014
We have applied a fast and high-yielding method for the parallel amidation of 4-[4-(2-methoxyphenyl)piperazin-1-yl]-butylamine yielding analogs of the partial dopamine receptor agonist BP 897. Using this amino scaffold prepared in solution and polymer-bound carboxylic acid equivalents, we have synthesized a series of high affinity dopamine D(3) receptor ligands. The novel compounds were obtained in good to excellent yield and purity. Biological evaluation included determination of binding affinities at hD(2S) and hD(3) receptor subtypes. From the 22 novel structures presented here, compound 4v showed high affinity (K(i) (hD(3)) 1.6nM) and a 136-fold preference for the D(3) receptor versus that for the D(2) receptor subtype. Our results suggest that this derivatization technique is a useful method to speed up structure-activity relationships studies on dopamine receptor subtype modulators. 相似文献
94.
Expression of mutated cationic trypsinogen reduces cellular viability in AR4-2J cells 总被引:1,自引:0,他引:1
Gaiser S Ahler A Gundling F Kruse ML Savkovic V Selig L Teich N Tomasini R Dagorn JC Mössner J Keim V Bödeker H 《Biochemical and biophysical research communications》2005,334(2):721-728
Mutations in the human cationic trypsinogen are associated with hereditary pancreatitis. The cDNA coding for human cationic trypsinogen was subcloned into the expression vector pcDNA3. The mutations R122H, N29I, A16V, D22G, and K23R were introduced by site directed mutagenesis. We constructed an expression vector coding for active trypsin by subcloning the cDNA of trypsin lacking the coding region for the trypsin activating peptide behind an appropriate signal peptide. Expression of protein was verified by Western blot and measurement of enzymatic activity. AR4-2J cells were transiently transfected with the different expression vectors and cell viability and intracellular caspase-3 activity were quantified. In contrast to wild-type trypsinogen, expression of active trypsin and mutated trypsinogens reduced cell viability of AR4-2J cells. Expression of trypsin and R122H trypsinogen induced caspase-3 activity. Acinar cells might react to intracellular trypsin activity by triggering apoptosis. 相似文献
95.
Palagi PM Walther D Quadroni M Catherinet S Burgess J Zimmermann-Ivol CG Sanchez JC Binz PA Hochstrasser DF Appel RD 《Proteomics》2005,5(9):2381-2384
Images obtained from high-throughput mass spectrometry (MS) contain information that remains hidden when looking at a single spectrum at a time. Image processing of liquid chromatography-MS datasets can be extremely useful for quality control, experimental monitoring and knowledge extraction. The importance of imaging in differential analysis of proteomic experiments has already been established through two-dimensional gels and can now be foreseen with MS images. We present MSight, a new software designed to construct and manipulate MS images, as well as to facilitate their analysis and comparison. 相似文献
96.
Despite the consolidation of the specialized proteomics literature around a few established journals, such as Proteomics, Molecular and Cellular Proteomics, and the Journal of Proteome Research, a lot of information is still spread in many different publications from different fields, such as analytical sciences, MS, bioinformatics, etc. The purpose of SPS' Digest is to gather a selection of proteomics articles, to categorize them, and to make the list available on a periodic basis through a web page and email alerts. 相似文献
97.
Leung KY Lescuyer P Campbell J Byers HL Allard L Sanchez JC Ward MA 《Proteomics》2005,5(12):3040-3044
A novel strategy consisting of cleavable Isotope-Coded Affinity Tag (cICAT) combined with MASCOT Distiller was evaluated as a tool for the quantification of proteins in "abnormal" patient plasma, prepared by pooling samples from patients with acute stroke. Quantification of all light and heavy cICAT-labelled peptide ion pairs was obtained using MASCOT Distiller combined with a proprietary software. Peptides displaying differences were selected for identification by MS. These preliminary results show the promise of our approach to identify potential biomarkers. 相似文献
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99.
Cariou B van Harmelen K Duran-Sandoval D van Dijk T Grefhorst A Bouchaert E Fruchart JC Gonzalez FJ Kuipers F Staels B 《FEBS letters》2005,579(19):4076-4080
The farnesoid X receptor (FXR) has been suggested to play a role in gluconeogenesis. To determine whether FXR modulates the response to fasting in vivo, FXR-deficient (FXR−/−) and wild-type mice were submitted to fasting for 48 h. Our results demonstrate that FXR modulates the kinetics of alterations of glucose homeostasis during fasting, with FXR−/− mice displaying an early, accelerated hypoglycaemia response. Basal hepatic glucose production rate was lower in FXR−/− mice, together with a decrease in hepatic glycogen content. Moreover, hepatic PEPCK gene expression was transiently lower in FXR−/−mice after 6 h of fasting and was decreased in FXR−/−hepatocytes. FXR therefore plays an unexpected role in the control of fuel availability upon fasting. 相似文献
100.
Miyara M Amoura Z Parizot C Badoual C Dorgham K Trad S Nochy D Debré P Piette JC Gorochov G 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(12):8392-8400
The immune defect that could account for the multisystemic involvement that characterizes systemic lupus erythematosus (SLE) remains unknown. We hypothesized that iterative disease flares correspond to a recurrent defect in the peripheral immune suppression exerted by naturally occurring T regulatory cells (Tregs). Surprisingly, Tregs isolated from lupus patients show the same phenotypic and functional characteristics as corresponding cells found in healthy controls. A decrease in the proportion of circulating Tregs among other CD4+ T cells is nevertheless evidenced in active patients when this group is compared with healthy controls (0.57 +/- 0.24%, n = 45 vs 1.29 +/- 0.38%, n = 82, p < 0.0001) or with inactive patients (1.22 +/- 0.67%, n = 62, p < 0.0001). In contrast, the proportion of Tregs in other systemic autoimmune diseases such as primary Sj?gren syndrome and inflammatory myopathy does not significantly differ from controls' values (1.15 +/- 0.46%, n = 21, p = 0.09 and 1.16 +/- 0.44%, n = 16, p = 0.43, respectively). Lupus Tregs do not accumulate in either the lymph nodes or the diseased kidneys and are not killed by a circulating soluble factor, but demonstrate in vitro a heightened sensitivity to Fas-induced apoptosis. Finally, we show that the extent of Treg depletion correlates with the clinical severity of the flare. SLE flares are therefore associated with a global Treg depletion and not with a phenomenon of tissue redistribution. In summary, we suggest that the physiopathology of SLE could be tied to a defect in the homeostatic control of the Treg subpopulation. 相似文献