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81.
Delphine Paolucci‐Jeanjean Marie‐Pierre Belleville Gilbert M Rios 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2001,76(3):273-278
Loss of enzyme activity is a problem associated with enzymatic reactions in continuous recycled membrane reactors (CRMR). It may result from catalyst leakage and also enzyme denaturation due to the effects of pH, temperature, shear effects or adsorption/deposit on membrane. In this study, the relative importance of these various factors has been assessed in order to reduce their adverse effects on starch hydrolysis in a CRMR. The effects of temperature and denaturation by adsorption/deposit on membrane were the most limiting phenomena. Reducing the temperature to overcome thermal denaturation was not a practical solution since this increases viscosity and thereby decreases permeate flux and reactor performance. Insofar that adsorption/deposit of enzymes on the membrane is directly linked to membrane fouling, back‐flushing or regularly purging retentate should reduce this phenomenon by lowering accumulation of high molecular weight products. © 2001 Society of Chemical Industry 相似文献
82.
Thioether Analogues of Disulfide‐Bridged Cyclic Peptides Targeting Death Receptor 5: Conformational Analysis,Dimerisation and Consequences for Receptor Activation 下载免费PDF全文
Dr. Karolina Pulka‐Ziach Dr. Valeria Pavet Neila Chekkat Dr. Karine Estieu‐Gionnet Roman Rohac Dr. Marie‐Charlotte Lechner Dr. Cristian R. Smulski Dr. Gabrielle Zeder‐Lutz Dr. Danièle Altschuh Dr. Hinrich Gronemeyer Prof. Dr. Sylvie Fournel Dr. Benoit Odaert Dr. Gilles Guichard 《Chembiochem : a European journal of chemical biology》2015,16(2):293-301
Cyclic peptides containing redox‐stable thioether bridges might provide a useful alternative to disulfide‐bridged bioactive peptides. We report the effect of replacing the disulfide bridge with a lanthionine linkage in a 16‐mer cyclic peptide that binds to death receptor 5 (DR5, TRAIL‐R2). Upon covalent oligomerisation, the disulfide‐bridged peptide has previously shown similar behaviour to that of TNF‐related apoptosis inducing ligand (TRAIL), by selectively triggering the DR5 cell death pathway. The structural and biological properties of the DR5‐binding peptide and its desulfurised analogue were compared. Surface plasmon resonance (SPR) data suggest that these peptides bind DR5 with comparable affinities. The same holds true for dimeric versions of these peptides: the thioether is able to induce DR5‐mediated apoptosis of BJAB lymphoma and tumorigenic BJELR cells, albeit to a slightly lower extent compared to its disulfide homologue. NMR analysis revealed subtle variation in the conformations of the two peptides and suggests that the thioether peptide is slightly less folded than its disulfide homologue. These observations could account for the different capability of the two dimers to cluster DR5 receptors on the cell surface and to trigger apoptosis. Nevertheless, our results suggest that the thioether peptide is a potential candidate for evaluation in animal models. 相似文献
83.
Oxidative Metabolism of Ferrocene Analogues of Tamoxifen: Characterization and Antiproliferative Activities of the Metabolites 下载免费PDF全文
Dr. Marie‐Aude Richard Dr. Didier Hamels Dr. Pascal Pigeon Dr. Siden Top Dr. Patrick M. Dansette Hui Zhi Shirley Lee Dr. Anne Vessières Dr. Daniel Mansuy Prof. Gérard Jaouen 《ChemMedChem》2015,10(6):981-990
Ferrociphenols have been found to have high antiproliferative activity against estrogen‐independent breast cancer cells. The rat and human liver microsome‐mediated metabolism of three compounds of the ferrocifen ( FC ) family, 1,1‐bis(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC1 ), 1‐(4‐hydroxyphenyl)‐1‐(phenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC2 ), and 1‐[4‐(3‐dimethylaminopropoxy)phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene ( FC3 ), was studied. Three main metabolite classes were identified: quinone methides ( QM s) deriving from two‐electron oxidation of FC s, cyclic indene products ( CP s) deriving from acid‐catalyzed cyclization of QM s, and allylic alcohols ( AA s) deriving from hydroxylation of FC s. These metabolites are generated by cytochromes P450 (P450s), as shown by experiments with either N‐benzylimidazole as a P450 inhibitor or recombinant human P450s. Such P450‐dependent oxidation of the phenol function and hydroxylation of the allylic CH2 group of FC s leads to the formation of QM and AA metabolites, respectively. Some of the new ferrociphenols obtained in this study were found to exhibit remarkable antiproliferative effects toward MDA‐MB‐231 hormone‐independent breast cancer cells. 相似文献
84.
Pierre‐Marie Nigay Ange Nzihou Claire E. White Winston O. Soboyejo 《Journal of the American Ceramic Society》2017,100(10):4748-4759
In this paper, the structure‐property relationships of a clay ceramic with organic additives (biomass and biochar) are investigated to develop an alternative material for thermal energy storage. The firing transformations were elucidated using X‐ray pair distribution function analysis, differential scanning calorimetry, and scanning electron microscopy. It was found that the biomass increased the porosity, which resulted in a decrease of the specific heat capacity. On the other hand, the biochar remained in the clay ceramic without any interaction with the clay matrix up to 950°C. The specific heat capacity of the clay ceramic increased from 1.20 to 1.49 kJ/kg·K for a 30 wt% addition of biochar. The clay ceramic with a 30 wt% addition of biochar also conserved a high flexural strength of 11.1 MPa compared to that of the clay ceramic without organic additives (i.e., 18.9 MPa). Furthermore, the flexural strength only decreased by 23% after 100 thermal cycles. The crack growth associated with the thermal fatigue was limited by crack bridging and crack trapping. Hence, the current results suggest that clay/biochar ceramics can be as efficient as molten salts in thermal energy storage with the added benefit of an ease of use in the physical form of bricks. 相似文献
85.
Design of New Cardanol Derivative: Synthesis and Application as Potential Biobased Plasticizer for Poly(lactide) 下载免费PDF全文
Fatima Hassouma Iulia Mihai Ludivine Fetzer Thierry Fouquet Jean‐Marie Raquez Abdelghani Laachachi Hicham Ibn Al Ahrach Philippe Dubois 《大分子材料与工程》2016,301(10):1267-1278
A novel biobased plasticizer made of cardanol is designed for poly(lactide) (PLA). This cardanol‐derived plasticizer, i.e., methoxylated hydroxyethyl cardanol (MeCard), is synthesized through methoxylation of the double bonds on the side chain of cardanol, and characterized by 1H NMR and mass spectrometry. The plasticization effect of MeCard on the molecular structure, morphology, thermal and mechanical properties of PLA is evaluated and compared to that of a commercial cardanol, i.e., hydroxyethyl cardanol (pCard). The plasticization efficiency of MeCard is demonstrated by a substantial decrease of the glass transition temperature and storage modulus together with a significant increase of the elongation at break as compared to neat PLA. Moreover, MeCard exhibits higher plasticization performance than pCard toward PLA. Such behavior is related to a higher miscibility and compatibility between PLA and MeCard thanks to the methoxylation of the double bonds on the side chain of cardanol as shown by SEM micrographs.
86.
Dr. Marie Monestier Peggy Charbonnier Dr. Christelle Gateau Dr. Martine Cuillel Faustine Robert Colette Lebrun Dr. Elisabeth Mintz Prof. Olivier Renaudet Dr. Pascale Delangle 《Chembiochem : a European journal of chemical biology》2016,17(7):590-594
Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes. 相似文献
87.
Dr. Tessa Lühmann Valerie Spieler Dr. Vera Werner Dr. Marie‐Gabrielle Ludwig Dr. Juliane Fiebig Prof. Dr. Thomas D. Mueller Prof. Dr. Dr. Lorenz Meinel 《Chembiochem : a European journal of chemical biology》2016,17(22):2123-2128
Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity. 相似文献
88.
Structure–Activity Relationships of JMV4463, a Vectorized Cathepsin D Inhibitor with Antiproliferative Properties: The Unique Role of the AMPA‐Based Vector 下载免费PDF全文
Dr. Lubomir L. Vezenkov Clément A. Sanchez Dr. Virginie Bellet Dr. Vincent Martin Dr. Marie Maynadier Dr. Nadir Bettache Prof. Vincent Lisowski Prof. Jean Martinez Dr. Marcel Garcia Dr. Muriel Amblard Dr. Jean‐François Hernandez 《ChemMedChem》2016,11(3):302-308
Cathepsin D (CathD) is overexpressed and secreted by several solid tumors and stimulates their growth, the mechanism of which is still not understood. In this context, the pepstatin bioconjugate JMV4463 [Ac‐arg‐O2Oc‐(Val)3‐Sta‐Ala‐Sta‐(AMPA)4‐NH2; O2Oc=8‐amino‐3,6‐dioxaoctanoyl, Sta=statine, AMPA=ortho‐aminomethylphenylacetyl], containing a new kind of cell‐penetrating vector, was previously shown to exhibit potent antiproliferative effects in vitro and to delay the onset of tumors in vivo. In this study, we performed a structure–activity relationship analysis to evaluate the significance of the inhibitor and vector moieties of JMV4463. By modifying both statine residues of pepstatin we found that the antiproliferative activity is correlated with CathD inhibition, supporting a major role of the catalytic activity of intracellular CathD in cancer cell proliferation. Replacing the vector composed of four AMPA units with other vectors was found to abolish cytotoxicity, although all of the conjugates enabled pepstatin transport into cells. In addition, the AMPA4 vector must be localized at the C terminus of the bioconjugate. The unexpected importance of the vector structure and position for cytotoxic action suggests that AMPA4 enables pepstatin to inhibit the proteolysis of critical CathD substrates involved in cell proliferation via a unique mechanism of action. 相似文献
89.
Rafaela Gladysz Prof. Dr. Anne‐Marie Lambeir Dr. Jurgen Joossens Prof. Dr. Koen Augustyns Prof. Dr. Pieter Van der Veken 《ChemMedChem》2016,11(5):467-476
Substrate activity screening (SAS) was presented a decade ago by Ellman and co‐workers as a straightforward methodology for the identification of fragment‐sized building blocks for enzyme inhibitors. Ever since, SAS and variations derived from it have been successfully applied to the discovery of inhibitors of various families of enzymatically active drug targets. This review covers key achievements and challenges of SAS and related methodologies, including the modified substrate activity screening (MSAS) approach. Special attention is given to the kinetic and thermodynamic aspects of these methodologies, as a thorough understanding thereof is crucial for successfully transforming the identified fragment‐sized hits into potent inhibitors. 相似文献
90.
Jonathan M. Polfus Wen Xing Marit Riktor Martin F. Sunding Paul Inge Dahl Sidsel M. Hanetho Tommy Mokkelbost Yngve Larring Marie‐Laure Fontaine Rune Bredesen 《Journal of the American Ceramic Society》2016,99(3):1071-1078
Dense symmetric membranes of CaTi0.85?xFe0.15MnxO3?δ (x = 0.1, 0.15, 0.25, 0.4) are investigated in order to determine the optimal Mn dopant content with respect to highest O2 flux. O2 permeation measurements are performed as function of temperature between 700°C–1000°C and as function of the feed side ranging between 0.01 and 1 bar. X‐ray photoelectron spectroscopy is utilized to elucidate the charge state of Mn, and synchrotron radiation X‐ray powder diffraction (SR‐XPD) is employed to investigate the structure symmetry and cell volume of the perovskite phase at temperatures up to 800°C. The highest O2 permeability is found for x = 0.25 over the whole temperature and ranges, followed by x = 0.4 above 850°C. The O2 permeability for x = 0.25 reaches 0.01 mL(STP) min?1 cm?1 at 925°C with 0.21 bar feed side and Ar sweep gas. X‐ray photoelectron spectroscopy indicates that the charge state of Mn changes from approx. +3 to +4 when x > 0.1, which implies that Mn mainly improves electronic conductivity for x > 0.1. The cell volume is found to decrease linearly with Mn content, which coincides with an increase in the activation energy of O2 permeability. These results are consistent with the interpretation of the temperature and dependency of O2 permeation. The sintering behavior and thermal expansion properties are investigated by dilatometry, which show improved sinterability with increasing Mn content and that the thermal expansion coefficient decreases from 12.4 to 11.9 × 10?6 K?1 for x = 0 and x = 0.25, respectively. 相似文献