26 research outputs found

    Multigram synthesis of an orthogonally-protected pentasaccharide for use as a glycan precursor in a <i>Shigella flexneri</i> 3a conjugate vaccine: application to a ready-for-conjugation decasaccharide

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    International audienceThe rapidly growing interest in carbohydrate-based bioactive molecules calls for strategies enabling the appropriate design and large-scale delivery of the glycan moiety. Herein, we describe the robust and high-yielding chemical synthesis of an orthogonally-protected pentasaccharide intended for use as a central building block in vaccine development against Shigella flexneri 3a. Elaborated from advanced crystalline intermediates and fine-tuned catalytic processes facilitating regio-and stereoselective conversions, a robust [2 + 3] strategy was designed, which avoided several tedious purifications and efficiently delivered multigram amounts of the target pentasaccharide. Conversion of this intermediate into a donor and a linker-equipped acceptor then merging then into the frame of a [5 + 5] glycosylation step furnished a decasaccharide encompassing one trichloroacetamide moiety per repeat. Chemoselective delevulination and subsequent Pd(OH) 2-mediated hydrogenolysis enabling concomitant hydrodechlorination and azide reduction gave the ready-for-conjugation dimer of the repeating unit of the O-antigen from S. flexneri 3a featuring the natural stoichiometric O-acetylation. The proof-of-concept was established, opening the way to larger S. flexneri 3a oligosaccharides and fine-tuned glycoconjugates

    Ab initio calculation of x-ray absorption of iron up to 3 Mbar and 8000 K

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    International audienceUsing ab initio simulations within the generalized gradient approximation, we calculate x-ray absorption near edge spectra (XANES) at the iron K edge throughout the high-pressure phase diagram and up to extreme density and temperature conditions that are representative of the Earth's inner core (up to 3 Mbar and 8000 K). We show that XANES spectra near the Fe K edge exhibit clear signatures for the different high-temperature, high-pressure phases of iron. This suggests that XANES spectroscopy might be used to resolve ongoing controversies regarding both the high-pressure melting curve of iron and the nature of the solid phases undergoing melting up to several Mbar. In contrast to diffraction measurements, it also offers a severe constraint for density functional theory predictions of the transport properties of iron by providing direct information on the electronic structure of iron at these extreme conditions

    Venomous auger snail Hastula (Impages) hectica (Linnaeus, 1758): Molecular phylogeny, foregut anatomy and comparative toxinology

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    The > 10,000 living venomous marine snail species [superfamily Conoidea Fleming, 1822] include cone snails (Conus), the overwhelming focus of research. Hastula hectica (Linnaeus, 1758), a venomous snail in the family Terebridae Morch, 1852 was comprehensively investigated. The Terebridae comprise a major monophyletic group within Conoidea. H. hectica has a striking radular tooth to inject venom that looks like a perforated spear; in Conus, the tooth looks like a hypodermic needle. H. hectica venom contains a large complement of small disulfide-rich peptides, but with no apparent overlap with Conus in gene superfamilies expressed. Although Conus peptide toxins are densely post-translationally modified, no post-translationally modified amino acids were found in any Hastula venom peptide. The results suggest that different major lineages of venomous molluscs have strikingly divergent toxinological and venom-delivery strategies. J. Exp. Zool. (Mol. Deu. Euol.) 308B: 744- 756, 2007. (c) 2007 Wiley-Liss, Inc

    Progress in warm dense matter study with applications to planetology

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    We present an overview of some recent theoretical and experimental results obtained on the properties of iron and silica at conditions encountered in planetary interiors. The first part is concerned with the development of x-ray absorption near edge spectroscopy in dynamical experiments using high-energy lasers as a tool to investigate phase transitions and structural changes at extreme pressure-temperature conditions for these two key constituents. The second part focuses on the development of a quasi-isentropic compression technique to achieve the pressure-temperature conditions anticipated in planetary interiors (3-10 Mbar, 5000-8000 K). The experiments were performed using the LULI, LLNL and LIL high-energy lasers' facilities. The experimental results are analyzed using first-principle simulations based on density functional theory

    The Herschel-SPIRE Legacy Survey (HSLS): the scientific goals of a shallow and wide submillimeter imaging survey with SPIRE

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    A large sub-mm survey with Herschel will enable many exciting science opportunities, especially in an era of wide-field optical and radio surveys and high resolution cosmic microwave background experiments. The Herschel-SPIRE Legacy Survey (HSLS), will lead to imaging data over 4000 sq. degrees at 250, 350, and 500 micron. Major Goals of HSLS are: (a) produce a catalog of 2.5 to 3 million galaxies down to 26, 27 and 33 mJy (50% completeness; 5 sigma confusion noise) at 250, 350 and 500 micron, respectively, in the southern hemisphere (3000 sq. degrees) and in an equatorial strip (1000 sq. degrees), areas which have extensive multi-wavelength coverage and are easily accessible from ALMA. Two thirds of the of the sources are expected to be at z > 1, one third at z > 2 and about a 1000 at z > 5. (b) Remove point source confusion in secondary anisotropy studies with Planck and ground-based CMB data. (c) Find at least 1200 strongly lensed bright sub-mm sources leading to a 2% test of general relativity. (d) Identify 200 proto-cluster regions at z of 2 and perform an unbiased study of the environmental dependence of star formation. (e) Perform an unbiased survey for star formation and dust at high Galactic latitude and make a census of debris disks and dust around AGB stars and white dwarfs
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