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141.
Dr. Youness Touati-Jallabe Dr. Thibault Tintillier Dr. Elodie Mauchauffée Dr. Jean-Luc Boucher Jérémy Leroy Booma Ramassamy Dr. Abdallah Hamzé Dr. Karima Mezghenna Amine Bouzekrini Claudia Verna Jean Martinez Dr. Anne-Dominique Lajoix Dr. Jean-François Hernandez 《ChemMedChem》2020,15(6):517-531
More than 160 arginine analogues modified on the C-terminus via either an amide bond or a heterocyclic moiety (1,2,4-oxadiazole, 1,3,4-oxadiazole and 1,2,4-triazole) were prepared as potential inhibitors of NO synthases (NOS). A methodology involving formation of a thiocitrulline intermediate linked through its side-chain on a solid support followed by modification of its carboxylate group was developed. Finally, the side-chain thiourea group was either let unchanged, S-alkylated (Me, Et) or guanidinylated (Me, Et) to yield respectively after TFA treatment the corresponding thiocitrulline, S-Me/Et-isothiocitrulline and N-Me/Et-arginine substrate analogues. They all were tested against three recombinant NOS isoforms. Several compounds containing a S-Et- or a S-Me-Itc moiety and mainly belonging to both the dipeptide-like and 1,2,4-oxadiazole series were shown to inhibit nNOS and iNOS with IC50 in the 1–50 μM range. Spectral studies confirmed that these new compounds interacted at the heme active site. The more active compounds were found to inhibit intra-cellular iNOS expressed in RAW264.7 and INS-1 cells with similar efficiency than the reference compounds L-NIL and SEIT. 相似文献
142.
Francine Morris Ryan Vierling Lauren Boucher Prof. Jürgen Bosch Prof. Caren L. Freel Meyers 《Chembiochem : a European journal of chemical biology》2013,14(11):1309-1315
1‐Deoxy‐D ‐xylulose 5‐phosphate (DXP) synthase catalyzes the first step in the nonmammalian isoprenoid biosynthetic pathway to form DXP from pyruvate and D ‐glyceraldehyde 3‐phosphate (D ‐GAP) in a thiamin diphosphate‐dependent manner. Its unique structure and mechanism distinguish DXP synthase from its homologues and suggest that it should be pursued as an anti‐infective drug target. However, few reports describe any development of selective inhibitors of this enzyme. Here, we reveal that DXP synthase catalyzes C? N bond formation and exploit aromatic nitroso substrates as active site probes. Substrate specificity studies reveal a high affinity of DXP synthase for aromatic nitroso substrates compared to the related ThDP‐dependent enzyme pyruvate dehydrogenase (PDH). Results from inhibition and mutagenesis studies indicate that nitroso substrates bind to E. coli DXP synthase in a manner distinct from that of D ‐GAP. Our results suggest that the incorporation of aryl acceptor substrate mimics into unnatural bisubstrate analogues will impart selectivity to DXP synthase inhibitors. As a proof of concept, we show selective inhibition of DXP synthase by benzylacetylphosphonate (BnAP). 相似文献
143.
水热沉积电压对C-AlPO_4涂层显微结构的影响 总被引:1,自引:1,他引:1
以方石英型磷酸铝(C-A1PO4)粉体为原料,异丙醇为溶剂,碘为荷电介质,采用水热电泳沉积方法在涂有SiC涂层的碳纤维增强碳(C/C-SiC复合材料表面制备了C-A1PO4外涂层.借助X射线衍射和扫描电镜表征了涂层的晶相组成和显微结构.研究了沉积电压对C-A1PO4涂层显微结构的影响,并测试了涂层的抗氧化性能.结果表明:在180~220V范围内,水热沉积电压对涂层的显微结构有较大的影响,220V时制备的涂层致密均匀.涂层的沉积量以及涂层与基体的结合强度随着沉积电压的升高而增加;单位面积沉积量与时间的二次方根之间符合线性关系.与包埋法制备的SiC涂层相比,水热电泳沉积法制备的C-A1PO4涂层具有更好的抗氧化性能,涂层样品在1500℃的空气中氧化37h后质量损失仅为0.53%. 相似文献
144.
注射成型中浇口形式对塑件质量的影响 总被引:3,自引:3,他引:3
用生产实例介绍了不同浇口形式及位置对塑料熔体在型腔中的填充模式和注射成型后塑件的内在机械物理性能及表观质量的影响。 相似文献
145.
Removal of N‐butanol from aqueous solutions by ion–exchange membranes containing organic counterions
The pervaporation of aqueous butanol solutions was investigated using thin‐film composite membranes composed of a poly(vinylidene fluoride) substrate coated with a sulfonated poly(2,6‐dimethyl‐1,4‐phenelene oxide) polymer. The polymer was ion‐exchanged with quaternary ammonium cations having aliphatic substituents of various chain lengths. The pervaporation of aqueous n‐butanol solutions using these membranes gave a permeate more concentrated in n‐butanol; therefore, they were alcohol‐selective. The separation factor increased and the permeate flux decreased as the chain lengths of the aliphatic substituents were increased. Hence, the mass‐transport properties of such membranes can be controlled or altered to yield some desired permselectivity by the introduction of a proper counterion. It was observed that the n‐butanol flux was small relative to the total flux and, therefore, the water flux dominated the total permeate flux. The degree of swelling of the membranes and its effect on membrane performance was investigated as well. As the n‐butanol content was increased, the swelling of the membranes increased greatly. High membrane swelling caused a reduction in the separation factor. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 47–58, 1999 相似文献
146.
147.
Ghisa L. Dumeige Y. Ngan Nguyen Thi Kim Boucher Y.G. Feron P. 《Lightwave Technology, Journal of》2009,27(8):1059-1059
In the above paper we did not accurately evaluate the Q-factors given in Table I. We give in the present table the corrected values. Captions of figures 11, 12, 13 and 15 must be changed using these new values: in the caption of Fig. 11 Qin t 4.81, Qout = 11.61 and Qout t = 3.18; in the caption of Fig. 12 Qout = 9.71 and Qout t = 1.85; in the caption of Fig. 13 Qout = 6.01 and Qout t 4.64; in the caption of Fig. 15 Qout = 5.86 and Qout t = 2.11. In the text, the best Q-factor increase in the lossly case of 4.72 dB obtained at 10 Gbit/s. 相似文献
148.
Alexandre Boucher 《Computers & Geosciences》2009,35(6):1151-1158
Using a complex training image (TI) for the single normal equation simulation (SNESIM) algorithm results in poor simulated realizations since that image contains trends and location specific patterns. By pooling all the TI patterns in a single search tree and not recording the relative locations of those patterns, some critical features of these complex TIs are lost.The search tree partitioning approach subdivides a large TI into imbricated, homogeneous, smaller images, called partition classes. Each of these partition classes has a corresponding search tree that can be utilized by the SNESIM algorithm. These partition classes are obtained by processing the TIs with spatial filters that are pattern sensitive. The resulting filter scores are then clustered into partition classes. All patterns within a partition class are recorded by a search tree; there is one tree per partition class. At each pixel along the simulation path, the partition class is retrieved first and used to select the appropriate search tree. That search tree contains the patterns relevant to that partition class.In practice, the partitioning approach adds flexibility in choosing a TI. TIs that were easier to obtain but traditionally too complex for simulation can now be considered as input to SNESIM. In many cases, it also significantly increases the simulation speed by searching a vector of smaller trees instead of a single large one. A plugin for the SGeMS software is provided. 相似文献
149.
Measurements of benzene concentration based on high-resolution laser absorption spectroscopy by use of the R(6) transition in the nu(4) fundamental vibrational band near 14.8 mum (676.6 cm(-1)) are reported. These measurements were performed with a tunable continuous-wave, mid-infrared spectroscopic light source that employs difference-frequency mixing of two Ti:sapphire lasers in a GaSe nonlinear optical crystal. A minimum benzene concentration detection of ~11.5 parts in 10(6) was realized at a reduced pressure of 40 mbars. 相似文献
150.
CA McGibbon DE Krebs CA Trahan SB Trippel RW Mann 《Canadian Metallurgical Quarterly》1999,14(1):52-58
The mitochondrial, inner-membrane-associated, reversible NADPH-->NAD transhydrogenase of adult Hymenolepis diminuta physiologically couples matrix-localized, NADP-specific "malic" enzyme with NADH-dependent anaerobic electron transport. Employing submitochondrial particles (SMP) as the source of enzyme activity and both spectrophotometric and fluorometric assessments, the present study made evident that in its catalysis of transhydrogenation between NADPH and NAD, the cestode enzyme engages in the concomitant transmembrane translocation of protons. As assessed spectrophotometrically, the catalysis of NADPH-dependent NAD reduction by H. diminuta SMP was stimulated significantly by carbonyl cyanide 3-chlorophenylhydrazone (CCCP), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), as well as by the protonophoric anthelmintic, niclosamide. In addition, N,N'-dicyclohexylcarbodiimide (DCCD) markedly diminished SMP-catalyzed hydride ion transfer between NADPH and NAD. The catalysis by SMP of concomitant, transhydrogenase-mediated proton translocation was evaluated more directly via fluorometric assays using 8-anilino-1-napthalenesulfonic acid (ANS) as the probe. These latter evaluations revealed a transhydrogenase-dependent enhancement of ANS fluorescence in accord with an intravesicular accumulation of protons. ANS fluorescence was quenched rapidly when the assay system was supplemented with CCCP, FCCP, or niclosamide. Consistent with the helminth transhydrogenase acting as a proton pump, transhydrogenase-mediated enhanced fluorescence also was inhibited by DCCD. Considered collectively, these data indicated, apparently for the first time for any invertebrate system, that the transhydrogenase, in catalyzing the NADPH-->NAD reaction, acts in the translocation of protons from the matrix to the intermembrane space mitochondrial compartment. 相似文献