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141.
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
142.
Roxana E. Teppa Daniel Petit Olga Plechakova Virginie Cogez Anne Harduin-Lepers 《International journal of molecular sciences》2016,17(8)
Cell surface of eukaryotic cells is covered with a wide variety of sialylated molecules involved in diverse biological processes and taking part in cell–cell interactions. Although the physiological relevance of these sialylated glycoconjugates in vertebrates begins to be deciphered, the origin and evolution of the genetic machinery implicated in their biosynthetic pathway are poorly understood. Among the variety of actors involved in the sialylation machinery, sialyltransferases are key enzymes for the biosynthesis of sialylated molecules. This review focus on β-galactoside α2,3/6-sialyltransferases belonging to the ST3Gal and ST6Gal families. We propose here an outline of the evolutionary history of these two major ST families. Comparative genomics, molecular phylogeny and structural bioinformatics provided insights into the functional innovations in sialic acid metabolism and enabled to explore how ST-gene function evolved in vertebrates. 相似文献
143.
Marie-Alix Pizzoccaro Martin Drobek Eddy Petit Gilles Guerrero Peter Hesemann Anne Julbe 《International journal of molecular sciences》2016,17(8)
Imidazolium bromide-based ionic liquids bearing phosphonyl groups on the cationic part were synthesized and grafted on γ-alumina (γ-Al2O3) powders. These powders were prepared as companion samples of conventional mesoporous γ-alumina membranes, in order to favor a possible transfer of the results to supported membrane materials, which could be used for CO2 separation applications. Effective grafting was demonstrated using energy dispersive X-ray spectrometry (EDX), N2 adsorption measurements, fourier transform infrared spectroscopy (FTIR), and special attention was paid to 31P and 13C solid state nuclear magnetic resonance spectroscopy (NMR). 相似文献
144.
It is well known that acidity, pH, of a solution accelerates the hydrolysis of soluble amides. Here we describe the unexpected result that weak small organic acids at low concentrations hydrolyze a polyamide at rates approximately twice that of a water HCl solution of the same pH. The effect of three small organic acids in dilute solutions, acetic, propanoic, and butanoic was studied. It is observed that the effect on the hydrolysis rate increases as the organic acid gets weaker. Butanoic, the weakest acid, has the strongest effect on increasing the hydrolysis rate. Measurements on the concentration of these acids in the polyamide reveal that there is a selective desire for these weak organic acids to diffuse into the polyamide. The concentration of these acids in the polyamide is found to be several multiples of the concentration in the water environment. And the acid concentration is highest for butanoic. The hydrolysis rate is shown to be governed by solubility, not pH of the water environment. The longer hydrocarbon tail on the carboxylic group increases its compatibility with the polyamide's monomer structure. Results are reported on the hydrolysis of polyamide-11 polymerized from aminoundecanoic acid, both neat and a commercial plasticized composition, placed in water at 100 °C and 120 °C under anaerobic conditions in high pressure glass tubes. 相似文献
145.
Pit Losch Anne‐Sophie Felten Patrick Pale 《Advanced Synthesis \u0026amp; Catalysis》2015,357(13):2931-2938
Zeolites with the right shape and acid site density and strength, such as certain ZSM‐5 forms, were able to cleanly decompose formic acid to carbon monoxide (CO), and the latter could be directly used in palladium‐catalyzed carbonylation reactions. A simple two‐reactor system was designed to produce CO conveniently and then further react this gas in a safe way. The two‐reactor system is particularly cheap, easy to set up and use. In addition, the carbonylation conditions without pressure allowed for very efficient CO incorporation, with only 1% of palladium(II) chloride (PdCl2) and Xantphos.
146.
The vacuolar aspartyl protease proteinase A (PrA) of Saccharomyces cerevisiae is encoded as a preproenzyme by the PEP4 gene and transported to the vacuole via the secretory route. Upon arrival of the proenzyme proPrA to the vacuole, active mature 42 kDa PrA is generated by specific proteolysis involving the vacuolar endoprotease proteinase B (PrB). Vacuolar activation of proPrA can also take place in mutants lacking PrB activity (prb1). Here an active 43 kDa species termed pseudoPrA is formed, probably by an autocatalytic process. When the PEP4 gene is overexpressed in wild-type cells, mature PrA can be found in the growth medium. We have found that prb1 strains overexpressing PEP4 can form pseudoPrA extracellularly. N-terminal amino acid sequence determination of extracellular, as well as vacuolar pseudoPrA showed that it contains nine amino acids of the propeptide, indicating a cleavage between Phe67 and Ser68 of the preproenzyme. This cleavage site is in accordance with the known substrate preference for PrA, supporting the notion that pseudoPrA is formed by autoactivation. When a multicopy PEP4 transformant of a prb1 mutant was grown in the presence of the aspartyl protease inhibitor pepstatin A, a significant level of proPrA was found in the growth medium. Our analyses show that overexpression of PEP4 leads to the secretion of proPrA to the growth medium where the zymogen is converted to pseudoPrA or mature PrA in a manner similar to the vacuolar processing reactions. Amino acid sequencing of secreted proPrA confirmed the predicted cleavage by signal peptidase between Ala22 and Lys23 of the preproenzyme. 相似文献
147.
148.
Jean-Denis Troadec Stphanie Gaig Manon Barbot Bruno Lebrun Rym Barbouche Anne Abysique 《International journal of molecular sciences》2022,23(2)
The avoidance of being overweight or obese is a daily challenge for a growing number of people. The growing proportion of people suffering from a nutritional imbalance in many parts of the world exemplifies this challenge and emphasizes the need for a better understanding of the mechanisms that regulate nutritional balance. Until recently, research on the central regulation of food intake primarily focused on neuronal signaling, with little attention paid to the role of glial cells. Over the last few decades, our understanding of glial cells has changed dramatically. These cells are increasingly regarded as important neuronal partners, contributing not just to cerebral homeostasis, but also to cerebral signaling. Our understanding of the central regulation of energy balance is part of this (r)evolution. Evidence is accumulating that glial cells play a dynamic role in the modulation of energy balance. In the present review, we summarize recent data indicating that the multifaceted glial compartment of the brainstem dorsal vagal complex (DVC) should be considered in research aimed at identifying feeding-related processes operating at this level. 相似文献
149.
Jerome Kluza Victoriane Peugnet Blanche Daunou William Laine Gwenola Kervoaze Gaëlle Rmy Anne Loyens Patrice Maboudou Quentin Fovez Corinne Grangette Isabelle Wolowczuk Philippe Gosset Guillaume Garon Philippe Marchetti Florence Pinet Muriel Pichavant Emilie Dubois-Deruy 《International journal of molecular sciences》2022,23(1)
Mitochondrial dysfunctions are implicated in several pathologies, such as metabolic, cardiovascular, respiratory, and neurological diseases, as well as in cancer and aging. These metabolic alterations are usually assessed in human or murine samples by mitochondrial respiratory chain enzymatic assays, by measuring the oxygen consumption of intact mitochondria isolated from tissues, or from cells obtained after physical or enzymatic disruption of the tissues. However, these methodologies do not maintain tissue multicellular organization and cell-cell interactions, known to influence mitochondrial metabolism. Here, we develop an optimal model to measure mitochondrial oxygen consumption in heart and lung tissue samples using the XF24 Extracellular Flux Analyzer (Seahorse) and discuss the advantages and limitations of this technological approach. Our results demonstrate that tissue organization, as well as mitochondrial ultrastructure and respiratory function, are preserved in heart and lung tissues freshly processed or after overnight conservation at 4 °C. Using this method, we confirmed the repeatedly reported obesity-associated mitochondrial dysfunction in the heart and extended it to the lungs. We set up and validated a new strategy to optimally assess mitochondrial function in murine tissues. As such, this method is of great potential interest for monitoring mitochondrial function in cohort samples. 相似文献
150.