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71.
Loïc Quinton Denis Servent Emmanuelle Girard Jordi Molgó Jean-Pierre Le Caer Christian Malosse El Ali Haidar Alain Lecoq Nicolas Gilles Julia Chamot-Rooke 《Analytical and bioanalytical chemistry》2013,405(15):5341-5351
Nicotinic acetylcholine receptors (nAChRs) are one of the most important families in the ligand-gated ion channel superfamily due to their involvement in primordial brain functions and in several neurodegenerative pathologies. The discovery of new ligands which can bind with high affinity and selectivity to nAChR subtypes is of prime interest in order to study these receptors and to potentially discover new drugs for treating various pathologies. Predatory cone snails of the genus Conus hunt their prey using venoms containing a large number of small, highly structured peptides called conotoxins. Conotoxins are classified in different structural families and target a large panel of receptors and ion channels. Interestingly, nAChRs represent the only subgroup for which Conus has developed seven distinct families of conotoxins. Conus venoms have thus received much attention as they could represent a potential source of selective ligands of nAChR subtypes. We describe the mass spectrometric-based approaches which led to the discovery of a novel α-conotoxin targeting muscular nAChR from the venom of Conus ermineus. The presence of several posttranslational modifications complicated the N-terminal sequencing. To discriminate between the different possible sequences, analogs with variable N-terminus were synthesized and fragmented by MS/MS. Understanding the fragmentation pathways in the low m/z range appeared crucial to determine the right sequence. The biological activity of this novel α-conotoxin (α-EIIA) that belongs to the unusual α4/4 subfamily was determined by binding experiments. The results revealed not only its selectivity for the muscular nAChR, but also a clear discrimination between the two binding sites described for this receptor. 相似文献
72.
As part of our study of the mesomorphic properties of glucopyranosides containing fluorinated chains, this paper focuses on an investigation of the liquid crystalline behaviour of nonaromatic compounds. The synthesis of eight single-tailed materials which contain a semiperfluoroalkyl chain linked to the polar glucose head group is described. Using polarized optical microscopy, DSC and X-ray diffraction all the materials were found to show only monomesomorphism, a smectic A phase with bimolecular layers. The thermal behaviour is discussed in comparison with the previously reported data on the series of parent compounds. 相似文献
73.
Bénédicte Dayde Claire Pierra Gilles Gosselin Dominique Surleraux Amadou Tidjani Ilagouma Jean-Noël Volle David Virieux Jean-Luc Pirat 《Tetrahedron letters》2014
This Letter describes the synthesis of racemic analogues of unnatural 2′-deoxy nucleoside with a phosphorus atom replacing the carbon atom in the 3′-position. A seven-step sequence was developed in racemic series to afford unnatural 3′-phospha-2′-deoxyfuranose nucleosides. The phospha nucleoside analogues were tested against HCV, but did not show any antiviral activity at a 10 μM maximum concentration used for the inhibition assays of analogues 2-T, 2-C and 4-Tα. 相似文献
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Armand Gellis Charline Kieffer Nicolas Primas Gilles Lanzada Michel Giorgi Pierre Verhaeghe Patrice Vanelle 《Tetrahedron》2014
We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald–Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the SNAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest. 相似文献
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Desulfurized gypsum (DG) as a soil modifier imparts it with bulk solid sulfite. The Fe(III)–sulfite process in the liquid phase has shown great potential for the rapid removal of As(III), but the performance and mechanism of this process using DG as a sulfite source in aqueous solution remains unclear. In this work, employing solid CaSO3 as a source of SO32−, we have studied the effects of different conditions (e.g., pH, Fe dosage, sulfite dosage) on As(III) oxidation in the Fe(III)–CaSO3 system. The results show that 72.1% of As(III) was removed from solution by centrifugal treatment for 60 min at near-neutral pH. Quenching experiments have indicated that oxidation efficiencies of As(III) are due at 67.5% to HO•, 17.5% to SO5•− and 15% to SO4•−. This finding may have promising implications in developing a new cost-effective technology for the treatment of arsenic-containing water using DG. 相似文献
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