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J Ignacio Andrés Jesús Alcázar José M Alonso Adolfo Díaz Javier Fernández Pilar Gil Laura Iturrino Encarna Matesanz Theo F Meert Anton Megens Victor K Sipido 《Bioorganic & medicinal chemistry letters》2002,12(2):249-253
Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described. 相似文献
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Position-dependent sequence elements downstream of AAUAAA are required for efficient rabbit beta-globin mRNA 3' end formation 总被引:46,自引:0,他引:46
We previously demonstrated that a critical 35 bp region 3' of the AAUAAA is required for rabbit beta-globin mRNA 3' end formation. Recently, we synthesized and tested sequence elements derived from this region. Here, we report that a GU-rich and a U-rich sequence element are both required for efficient rabbit beta-globin mRNA 3' end formation. The efficiency of processing is restored to the wild-type level when the two elements are placed together and is greatly diminished when only one element is present. The level of 3' end formation is also decreased when the distance between the two elements is expanded. These results demonstrate that the GU-rich and U-rich elements function synergistically to restore efficient mRNA 3' end formation and that they most likely form a single requisite sequence 3' of the AAUAAA. Furthermore, we show that the effect of the GU-rich and U-rich sequence elements is position-dependent. 相似文献
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Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom 总被引:13,自引:0,他引:13
B M Olivera L J Cruz V de Santos G W LeCheminant D Griffin R Zeikus J M McIntosh R Galyean J Varga W R Gray 《Biochemistry》1987,26(8):2086-2090
The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from omega-conotoxins from Conus geographus. Total synthesis of omega-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although omega-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of omega-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two omega-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neuronal Ca2+ channels. 相似文献
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Drosophila buzzatii feeds and breeds on the decaying cladodes and fruits of several species of Opuntia (prickly pear) which contain significant levels of ethanol and isopropanol. The potential influence of these two alcohols on the inversion polymorphism of the second and fourth chromosomes was investigated in ten experimental populations with different amounts of alcohol (either ethanol or isopropanol) added to the culture medium. All populations were started with the offspring of 29 wild females collected at Adeje (Tenerife, Canary Islands) and their genetic composition was monitored for about two years (more than 30 generations). Consistent changes in the frequency of most second- and fourth-chromosome arrangements occurred in all populations including those without alcohol (control). The comparison of inversion frequency through the various treatments revealed a significant influence of the alcohol on the frequency changes of the four second-chromosome arrangements. Moreover, this influence was of a different type for every one of them, sometimes with opposite effects between alcohols and/or concentrations. These results indicate genetic differentiation among second-chromosome arrangements with regard to alcohol and suggest that the alcohol heterogeneity found in the species' trophic niche may play an important role in the maintenance of this polymorphism and also in the recent historical changes in the frequency of some arrangements associated with colonization.This paper is number X of the series The evolutionary history of Drosophila buzzatii. 相似文献
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Chicken liver mitochondrial aspartate aminotransferase was found to be located in the intermembrane space and bound to the inner mitochondrial membrane. Purification of two mitochondrial fractions containing aspartate aminotransferase activity was performed. Both fractions showed similar chromatographic behaviour and identical isoelectric point and molecular weight values. There were no significant differences in the general kinetic mechanism, Km values, substrates inhibition and effect of various anions on the activity of mitochondrial aspartate aminotransferase purified from both fractions. 相似文献