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11.
Structure–Activity Relationships of JMV4463, a Vectorized Cathepsin D Inhibitor with Antiproliferative Properties: The Unique Role of the AMPA‐Based Vector
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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
12.
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
13.
Fei Huang Tomáš Halenkovič Marion Baillieul Virginie Nazabal Petr Němec Josef Havel 《Journal of the American Ceramic Society》2022,105(3):1992-2000
Quaternary germanium-antimony-selenium-tellurium (Ge-Sb-Se-Te) thin films deposited from Ge19.4Sb16.7Se63.9−xTex (x = 5, 10, 15, and 20) glass-ceramics targets by radio frequency magnetron sputtering were studied using laser ablation quadrupole ion trap time of flight mass spectrometry. Binary, ternary, and quaternary GeaSbbSecTed clusters were formed and their stoichiometry was determined. By comparison of the clusters obtained from quaternary Ge-Sb-Se-Te thin films and those from ternary Ge-Sb-Te materials, we found that Ge-Te species are not detected from the quaternary system. Furthermore, Ge-Se and Se-Te species are missing in mass spectra generated from Ge-Sb-Se-Te thin films. From the Ge-Sb-Se-Te thin films, 16 clusters were detected while ternary Ge-Sb-Se glasses yielded 26 species. This might be considered as a signal of higher stability of Ge-Sb-Se-Te thin films which is increasing with a higher content of Te. The missing (Se2+, GeaSb+ (a = 1–4), and GeSec+ (c = 1, 2)) and new (Ge+ and SbbTe+ (b = 1–3)) clusters may indicate that some of the structural features of the films (Ge2Se6/2 and Se2Sb-SbSe2) were replaced by (GeSe4−xTex and SbSe3−xTex) ones. In addition, when comparing the stoichiometry of clusters formed from Ge-Sb-Se-Te thin films with those from the mixtures of the elements, only Sb3+ and SbSe+ were observed in both cases. The knowledge gained concerning clusters stoichiometry contributes to the elucidation of the processes proceeding during plasma formation used for the chalcogenide thin films deposition. 相似文献
14.
Sophie Perrier dHauterive Romann Close Virginie Gridelet Marie Mawet Michelle Nisolle Vincent Geenen 《International journal of molecular sciences》2022,23(3)
Human chorionic gonadotropin (hCG) has four major isoforms: classical hCG, hyperglycosylated hCG, free β subunit, and sulphated hCG. Classical hCG is the first molecule synthesized by the embryo. Its RNA is transcribed as early as the eight-cell stage and the blastocyst produces the protein before its implantation. This review synthetizes everything currently known on this multi-effect hormone: hCG levels, angiogenetic activity, immunological actions, and effects on miscarriages and thyroid function. 相似文献
15.
Melinda OlivierParastesh Pirasteh Jean-Louis DoualanPatrice Camy Hervé LhermiteJean-Luc Adam Virginie Nazabal 《Optical Materials》2011,33(7):980-984
Praseodymium doped Fluoride glasses were studied in order to fabricate compact solid state laser sources emitting in the visible range for lighting application and for quantum information processing. The objective of this study is focused on red, green and orange emissions. ZBLA bulk glasses (57%ZrF4 - 34%BaF2 - (5 − x)%LaF3 - 4%AlF3 - x%PrF3) have been synthesized under dry argon atmosphere. Physicochemical and optical properties such as density, glass transition temperature, composition, transmission and refractive index have been investigated. Spectroscopic studies have been performed to optimize the rare earth doping level in order to reach the best compromise respecting a good optical quality, a highest lifetime and efficient emission intensity at 635, 605 and 520 nm. Spectroscopic measurements have been carried out on bulk samples with Pr3+ concentrations ranging from 0.1 to 3 mol% and first characterizations of ion exchanged Pr: ZBLA waveguides are reported. 相似文献
16.
Virginie Boscher Renaud Helleboid Thierry Lasuye Bernard Stasik Gérard Riess 《Polymer International》2009,58(10):1209-1216
BACKGROUND: Poly[(vinyl alcohol)‐co‐(vinyl acetate)] (PVA) copolymers obtained by partial hydrolysis of poly(vinyl acetate) are currently used as industrial stabilizers in the suspension polymerization of vinyl chloride monomer (VCM). Their molecular characteristics, mainly the average degree of hydrolysis (DH ) and average degree of polymerization (DPw ), have a major influence on the monomer droplet size and the properties of the final poly(vinyl chloride) resin. RESULTS: The average droplet size and size distribution of chlorobutane/water emulsions, as a model system for VCM/water emulsions, were studied using acoustic attenuation spectroscopy on‐line with an agitated laboratory reactor. The emulsions were stabilized by PVA with DH values between 73 and 88 mol% and DPw values between 450 and 2500. The effects of agitation speed, stirring time and concentration of the PVA copolymers were investigated. An attempt was made to correlate the interfacial tension and the droplet size. CONCLUSION: On‐line acoustic spectroscopy appears to be a suitable technique for the real‐time control of the droplet size of monomer suspensions. The advantages and limitations of the technique are outlined. The validity and the application limits of the commonly cited correlation between the droplet size and the Weber number are established for polymeric surfactant‐stabilized emulsions. Copyright © 2009 Society of Chemical Industry 相似文献
17.
Philippe Roger Sylvie Grard Virginie Burckbuchler Laëtitia Renaudie Patrick Judeinstein 《Polymer》2007,48(26):7539-7545
In this work, the influence of the incorporation of a small amount of carbohydrate-containing monomer N-acryloyllactosylamine (LAM) on the swelling behavior of covalently-crosslinked polyacrylamide hydrogels in water has been reported. The incorporation of LAM into the copolymer was assessed by ATR–FTIR and thermogravimetric experiments. The main result is that the equilibrium water uptake was significantly decreased as soon as the hydrogel contained LAM considering a constant amount of crosslinking agent. The greatest difference of water uptakes between carbohydrate-free hydrogel and carbohydrate-containing hydrogel occurred for the lowest crosslinker amount of 1 mol%. In that case, the value of the water uptake reached 56-fold for the carbohydrate-free hydrogel and decreased down to 41-fold for the 10 mol% LAM hydrogel. Additional NMR experiments were used to measure the amount of non-crystallizable water which was higher for carbohydrate-free hydrogel than that for lactose-containing hydrogel confirming the water uptake results. 相似文献
18.
Michael A. McNeil Maithili IyerStephen Meyers Virginie E. LetschertJames E. McMahon 《Energy Policy》2008
The economy of the world's second most populous country continues to grow rapidly, bringing prosperity to a growing middle class while further straining an energy infrastructure already stretched beyond capacity. At the same time, efficiency policy initiatives have gained a foothold in India, and promise to grow in number over the coming years. This paper considers the maximum cost-effective potential of efficiency improvement for key energy-consuming products in the Indian context. The products considered are: household refrigerators, window air conditioners, motors and distribution transformers. Together, these products account for about 27% of delivered electricity consumption in India. The analysis estimates the minimum Life-Cycle Cost option for each product class, according to use patterns and prevailing customer marginal rates in each sector. This option represents an efficiency improvement ranging between 12% and 60%, depending on product class. If this level of efficiency was achieved starting in 2010, we estimate that total electricity consumption in India could be reduced by 4.7% by 2020, saving over 74 million tons of oil equivalent and over 246 million tons of carbon dioxide emissions. Net present financial savings of this efficiency improvement totals 8.1 billion dollars. 相似文献
19.
This paper presents a methodology for modeling residential appliance uptake as a function of root macroeconomic drivers. The analysis concentrates on four major energy end uses in the residential sector: refrigerators, washing machines, televisions and air conditioners. The model employs linear regression analysis to parameterize appliance ownership in terms of household income, urbanization and electrification rates according to a standard binary choice (logistic) function. The underlying household appliance ownership data are gathered from a variety of sources including energy consumption and more general standard of living surveys. These data span a wide range of countries, including many developing countries for which appliance ownership is currently low, but likely to grow significantly over the next decades as a result of economic development. The result is a ‘global’ parameterization of appliance ownership rates as a function of widely available macroeconomic variables for the four appliances studied, which provides a reliable basis for interpolation where data are not available, and forecasting of ownership rates on a global scale. The main value of this method is to form the foundation of bottom-up energy demand forecasts, project energy-related greenhouse gas emissions, and allow for the construction of detailed emissions mitigation scenarios. 相似文献
20.
Yamine Ait Ameur Frédéric Boniol Virginie Wiels 《International Journal on Software Tools for Technology Transfer (STTT)》2010,12(1):1-7
Nowadays, it is well accepted that the development of critical systems involves the use of formal methods. One of the major
fields where these methods made a lot of progress are the avionics, aerospace and more generally transport areas. Several
methods, tools and techniques have been applied for the development of such systems in different parts of the world, and they
have been actually put into practice during the development of specific aircraft programs. The aim of this introductory article
and of this STTT special issue is to propose a brief overview of the state-of-the-art of current researches in formal methods
applied to the development of avionics and aerospace systems and more broadly to take stock of the integration of formal methods
in the aerospace industry. 相似文献