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排序方式: 共有210条查询结果,搜索用时 15 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
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CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling 总被引:8,自引:0,他引:8 下载免费PDF全文
Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors. 相似文献
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The endosome-associated protein Hrs inhibits the homotypic fusion of early endosomes. A helical region of Hrs containing a Q-SNARE motif mediates this effect as well as its endosomal membrane association via SNAP-25, an endosomal receptor for Hrs. Hrs inhibits formation of an early endosomal SNARE complex by displacing VAMP-2 from the complex, suggesting a mechanism by which Hrs inhibits early endosome fusion. We examined the regulation of endosomal SNARE complexes to probe how Hrs may function as a negative regulator. We show that although NSF dissociates the VAMP-2.SNAP-25.syntaxin 13 complex, it has no effect on the Hrs-containing complex. Whereas Ca(2+) dissociates the Hrs-containing complex but not the VAMP-2-containing SNARE complex. This is the first demonstration of differential regulation of R/Q-SNARE and all Q-SNARE-containing SNARE complexes. Ca(2+) also reverses the Hrs-induced inhibition of early endosome fusion in a tetanus toxin-sensitive manner and removes Hrs from early endosomal membranes. Moreover, Hrs inhibition of endosome fusion and its endosomal localization are sensitive to bafilomycin, implying a role for luminal Ca(2+). Thus, Hrs may bind a SNARE protein on early endosomal membranes negatively regulating trans-SNARE pairing and endosomal fusion. The release of Ca(2+) from the endosome lumen dissociates Hrs, allowing a VAMP-2-containing complex to form enabling fusion. 相似文献
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The aim of the study was to describe the peculiarities of pike spawning in mesotrophic Lake Rubikiai, to determine the spawning population structure and evaluate the influence of some environmental factors on year-class strength formation. The data were collected in April and May (1994–2011). A total of 1586 individuals were caught. The age of pike ranged from 1 to 12 years; 2–5-yearold males (96.0%) and 3–8-year-old females (89.1%) prevailed. The overall sex ratio of females to males was 1:4.1. One-year-old spawning males (26.5–28.5 cm) and two-year-old spawning females (31.5–35.5 cm) constituted 2.1% and 2.6%, respectively. Water temperature during the spawning period was relatively stable, between 4 and 6°C, during March and increased slightly towards 10°C in the middle of April. No correlation was observed between female length and spawning date. Year-class strength did not correlate with the last day of ice presence and the minimal water level at the end of spawning (WLmin), but statistically significantly negatively correlated with the maximum water level at the beginning of spawning (WLmax) and the difference between WLmax and WLmin. The mean annual survival rate for pike (aged ≥2) was 0.74 and the mean annual instantaneous mortality rate was 0.45. 相似文献
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A Ase O Vindrola R Aloyz M Inés R Vida S Finkielman V Nahmod 《Biochemical and biophysical research communications》1989,158(3):790-796
The association of endogenous synenkephalin and met-enkephalin containing peptides with the membrane of bovine chromaffin granules and physicochemical characteristics of this association were studied. The associated materials were only released at a non physiological pH range and this effect was enhanced with growing salt concentrations (0.5, 1.0 and 2.0 M KSCN). A higher peptide dissociation occurred with membrane solubilizing agents (SDS greater than Triton X-100 greater than digitonin). In microsomes the materials dissociated with 2 M KSCN (pH 7.4) corresponded to peptides larger than 12.0 kDa, while in granules corresponded to molecules smaller than 8.5 kDa, displaying synenkephalin and met-enkephalin immunoreactivities. These data suggest that some sequence of the C-terminal portion of synenkephalin may be responsible for the association of proenkephalin derived peptides with microsome and granule membranes. 相似文献
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Relevance of Local Flexibility Near the Active Site for Enzymatic Catalysis: Biochemical Characterization and Engineering of Cellulase Cel5A From Bacillus agaradherans 下载免费PDF全文
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