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191.
Marchand P Le Borgne M Na YM Pagniez F Abdala H Le Baut G Le Pape P 《Journal of enzyme inhibition and medicinal chemistry》2002,17(6):353-358
The goal of the present study was to evaluate several azolyl-substituted indoles as new antileishmanial agents. Ten 3-(alpha-azolylbenzyl)indoles have been synthesized using Friedel-Crafts acylation as a key-step. All the target compounds were found to display high levels of activity when tested against Leishmania mexicana promastigotes in vitro. The most active compounds, showing an IC50 < 1 microM, were 5-bromo-1-ethyl-3-[(2,4-dichlorophenyl)(1H-imidazol-1-yl)methyl]-1H-indole 15 and its triazole analogue 17. Four representative compounds 15, 17, 22 and, 23 were also tested against intracellular amastigotes of L. mexicana using ketoconazole and meglumine antimoniate as reference compounds, the results of which are discussed. 相似文献
192.
Le Flem G Dupradeau FY Pujol JP Monti JP Bogdanowicz P 《Bioorganic & medicinal chemistry》2002,10(7):2111-2117
The design and total synthesis of a novel insulin A-chain mutant, analogue 3, is reported. In this compound, the cysteines implied in the two insulin inter-chain disulfide bridges are replaced by two serines (residues Ser(A7) and Ser(A20)) and the intra-A-chain disulfide bridge (residues Cys(A6) and Cys(A11)) is conserved. This A-chain analogue (3) has been tested in three in vitro cell culture assays, using insulin as a reference. The data clearly showed that analogue 3 mimics insulin effects on DNA synthesis, glucose uptake and glycogen synthesis without loss of potency as compared to insulin. To our knowledge, these are the first results showing that an isolated insulin chain displays functional properties similar to those of insulin. The implication of these new findings in insulin structure-function relationships and in a 'mini-insulin' structure determination is discussed. 相似文献
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196.
Nonsense-mediated mRNA decay (NMD) in mammalian cells depends on phosphorylation of Upf1, an RNA-dependent ATPase and 5'-to-3' helicase. Upf1 phosphorylation is mediated by Smg1, a phosphoinositol 3-kinase-related protein kinase. Here, we describe a human protein, which we call hSmg5/7a, that manifests similarity to Caenorhabditis elegans NMD factors CeSMG5 and CeSMG7, as well as two Drosophila melanogaster proteins that are also similar to the C. elegans NMD factors. Results indicate that hSmg5/7a functions in the dephosphorylation of Upf1. Furthermore, hSmg5/7a copurifies with Upf1, Upf2, Upf3X, Smg1, and the catalytic subunit of protein phosphatase 2A. We also demonstrate that Upf2, another factor involved in NMD, is a phosphoprotein. However, hSmg5/7a plays no role in the dephosphorylation of Upf2. These data indicate that hSmg5/7a targets protein phosphatase 2A to Upf1 but not Upf2. Results of Western blotting reveal that hSmg5/7a is mostly cytoplasmic in HEK293T cells. 相似文献
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198.
André C Jacquot Y Truong TT Thomassin M Robert JF Guillaume YC 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,796(2):267-281
The mechanisms of (i) the binding of two sex-hormones (i.e. progesterone and beta-estradiol) to human serum albumin (HSA) and (ii) the progesterone displacement of its HSA binding cavity by beta-estradiol were studied by biochromatography using three different methods. In the first time, zonal elution method was used to prove the direct competition effect between the two sex-hormone. In the second time, the competition effect between beta-estradiol and progesterone to bound on the same HSA site was analysed by the competitive bi-Langmuir approach. Finally, the thermodynamic data of these two binding processes were studied. The Gibbs free energy value (Delta(approximately)G degrees) of the displacement equilibrium was negative demonstrating that beta-estradiol displaced progesterone of its HSA binding cavity. Moreover, the effect of two chloride modifiers (i.e. Na(+), Mg(2+)) on these two binding processes were analysed. Results showed that in the salt biological concentration ranges, the Mg(2+) cation enhanced strongly the bioavailable progesterone, whereas the Na(+) cation interacted slowly on the progesterone displacement of its HSA binding site by beta-estradiol. This study showed that it must be useful to carry out more in vivo test on the magnesium supplementation effect for women who suffer from estrogen dominance syndrome. 相似文献
199.
Binz PA Abdi F Affolter M Allard L Barblan J Bhardwaj S Bienvenut WV Bulet P Burgess J Carrette O Corthals G Delalande F Diemer H Favreau P Giuliano E Gueguen Y Guillaume E Hahner S Man P Michalet S Neri D Noukakis D Palagi P Paroutaud P Pimenta DC Quadroni M Resemann A Richert S Rybak J Sanchez JC Scherl A Scheurer S Schweiger Hufnagel U Siethoff C Suckau D van Dorsselaer A Wagner Redeker W Walter N Stöcklin R 《Proteomics》2003,3(8):1562-1566
After the success of the mass spectrometry (MS) round table that was held at the first Swiss Proteomics Society congress (SPS'01) in Geneva, the SPS has organized a proteomics application exercise and allocated a full session at the SPS'02 congress. The main objective was to encourage the exchange of expertise in protein identification, with a focus on the use of mass spectrometry, and to create a bridge between the users' questions and the instrument providers' solutions. Two samples were sent to fifteen interested labs, including academic groups and MS hardware providers. Participants were asked to identify and partially characterize the samples. They consisted of a complex mixture of peptide/proteins (sample A) and an almost pure recombinant peptide carrying post-translational modifications (sample B). Sample A was an extract of snake venom from the species Bothrops jararaca. Sample B was a recombinant and modified peptide derived from the shrimp Penaeus vannamei penaeidin 3a. The eight labs that returned results reported the use of a wide range of MS instrumentation and techniques. They mentioned a variety of time and manpower allocations. The origin of sample A was generally identified together with a number of database protein entries. The difficulty of the sample identification lay in the incomplete knowledge of the Bothrops species genome sequence and is discussed. Sample B was generally and correctly identified as penaeidin. However, only one group reported the full primary structure. Interestingly, the approaches were again varied and are discussed in the text. 相似文献
200.
The Pyrenean brown bear (Ursus arctos) population is considered as one of the most seriously threatened with extinction in Western Europe. To assess its viability and possible needs of augmentation, we develop deterministic and stochastic stage-structured demographic models. The deterministic model reveals that a bear population cannot have a high annual growth rate and is particularly sensitive to breeder survival. High demographic parameters appear to be crucial to population persistence, especially for a small population that remains vulnerable to demographic and environmental stochasticities. The Pyrenean population cannot therefore be considered as viable. Successful conservation strategies for this population would require releasing more bears in both sub-populations in the near future. 相似文献