Herein, we discuss how, why,and when cascade complexation reactions produce stable, mononuclear, luminescent ternary complexes, by considering the binding of exafluoroacetylacetonate anions (hfac-) and neutral, semi-rigid, tridentate, 6-bis(benzimidazol-2-yl)pyridine ligands (Lk) to trivalent lanthanide atoms (LnIII). The solid-state structures of Ln(Lk)ACHTUNGTRENUNG(hfac)3] (Ln=La, Eu, Lu) showed that [Ln-ACHTUNGTRENUNG(hfac)3] behaved as a neutral six-coordinate lanthanide carrier with remarkable properties: 1) the strong cohesion between the trivalent cation and the didentate hfac anions prevented salt dissociation; 2) the electron-withdrawing trifluoromethyl substituents limited charge-neutralization and favored cascade complexation with Lk; 3) nine-coordination was preserved for [Ln(Lk)-ACHTUNGTRENUNG(hfac)3] for the complete lanthanide series, whilst a counterintuitive trend showed that the complexes formed with the smaller lanthanide elements were estabilized. Thermodynamic and NMR spectroscopic studies in solution confirmed that these characteristics were retained for solvated molecules, but the operation of concerted anion/ ligand transfers with the larger cations induced subtle structural variations. Combined with the strong red photoluminescence of Eu(Lk)ACHTUNGTRENUNG(hfac)3], the ternary system LnIII/hfac-/Lk is a promising candidate for the planned metalloading of preformed multi-tridentate polymers.
Meteoritics & Planetary Science (2012) sous presse – doi:10.1111/j.1945-5100.2012.01355.x
Résumé :
Analyses by the Mars Exploration Rover (MER), Spirit, of Martian basalts from Gusev crater show that they are chemically very different from terrestrial basalts, being characterized in particular by high Mg- and Fe-contents. To provide suitable analog basalts for the International Space Analogue Rockstore (ISAR), a collection of analog rocks and minerals for preparing in situ space missions, especially, the upcoming Mars mission MSL-2011 and the future international Mars-2018 mission, it is necessary to synthesize Martian basalts. The aim of this study was therefore to synthesize Martian basalt analogs to the Gusev crater basalts, based on the geochemical data from the MER rover Spirit. We present the results of two experiments, one producing a quench-cooled basalt (<1 h) and one producing a more slowly cooled basalt (1 day). Pyroxene and olivine textures produced in the more slowly cooled basalt were surprisingly similar to spinifex textures in komatiites, a volcanic rock type very common on the early Earth. These kinds of ultramafic rocks and their associated alteration products may have important astrobiological implications when associated with aqueous environments. Such rocks could provide habitats for chemolithotrophic microorganisms, while the glass and phyllosilicate derivatives can fix organic compounds.
Journal of Proteome Research (sous presse) doi : 10.1021/pr201239t
Résumé :
The PEBP (phosphatidylethanolamine-binding protein) family is a large group of proteins whose human member, hPEBP1, has been shown to play multiple functions, influencing intracellular signaling cascades, cell cycle regulation, neurodegenerative processes, and reproduction. It also acts, by an unknown mechanism, as a metastasis suppressor in a number of cancers. A more complete understanding of its biological role is thus necessary. As the yeast Saccharomyces cerevisiae is a powerful and easy to handle model organism, we focused on Tfs1p, the yeast ortholog of hPEBP1. In a previous study based on a two-hybrid approach, we showed that Tfs1p interacts and inhibits Ira2p, a GTPase Activating Protein (GAP) of the small GTPase Ras. In order to further characterize the molecular functions of Tfs1p, we undertook the identification of protein complexes formed around Tfs1p using a targeted proteomics approach. Complexed proteins were purified by tandem-affinity, cleaved with trypsin, and identified by nanoflow liquid chromatography coupled with tandem mass spectrometry. Overall, 14 new interactors were identified, including several proteins involved in intermediate metabolism. We confirmed by co-immunoprecipitation that Tfs1p interacts with Glo3p, a GAP for Arf GTPases belonging to the Ras superfamily of small GTPases, indicating that Tfs1p may be involved in the regulation of another GAP. We similarly confirmed the binding of Tfs1p with the metabolic enzymes Idp1p and Pro1p. Integration of these results with known functional partners of Tfs1p shows that two subnetworks meet through the Tfs1p node, suggesting that it may act as a bridge between cell signaling and intermediate metabolism in yeast.
Vandamme, M., Robert, E., Lerondel, S., Sarron, V., Ries, D., Dozias, S., Sobilo, J., Gosset, D., Kieda, C., Legrain, B., Pouvesle, J.M., and Le Pape, A.
Non-thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT-116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.
Hypoxia, a critical parameter of the tumor microenvironment, controls endothelial/tumor cell interactions and is the key to tumor angiogenesis development. Under hypoxic stress, tumor cells produce factors that promote angiogenesis, vasculogenesis, tumor cell motility, metastasis and cancer stem cell selection.
Targeting tumor vessels is a therapeutic strategy that has lately been fast evolving from antiangiogenesis to vessel normalization as discussed in this review. We shall focus on the pivotal role of endothelial cells within the tumor microenvironment, the specific features and the part played by circulating endothelial precursors cells. Attention is stressed on their recruitment to the tumor site and their role in tumor angiogenesis where they are submitted to miRNAs-mediated de/regulation. Here the compensation of the tumor deregulated angiogenic miRNAs – angiomiRs – is emphasized as a potential therapeutic approach. The strategy is to over express anti-angiomiRs in the tumor angiogenesis site upon selective delivery by precursor endothelial cells as miRs carriers.
ACS Chemical Biology – Date de publication sur le web : 25 janvier 2012
Abstract:
Changes in glycosylation are correlated to disease and associated with differentiation processes. Experimental tools are needed to investigate the physiological implications of these changes either by labeling of the modified glycans or by blocking their biosynthesis. N–acetylgalactosamine (GalNAc) is a monosaccharide widely encountered in glycolipids, proteoglycans and glycoproteins; once taken up by cells it can be converted through a salvage pathway to UDP–GalNAc which is further used by glycosyltransferases to build glycans. In order to find new reporter molecules able to integrate into cellular glycans, synthetic analogs of GalNAc were prepared and tested as substrates of both enzymes acting sequentially in the GalNAc salvage pathway, the galactokinase 2 (GK2) and the uridylpyrophosphorylase AGX1. Detailed in vitro assays identified the GalNAc analogs which can be transformed into sugar nucleotides and revealed several bottlenecks in the pathway: a modification on C6 is not tolerated by GK2; AGX1 can use all products of GK2 although with various efficiencies; all analogs transformed into UDP-GalNAc analogs except those with alterations on C4 are substrates for the polypeptide GalNAc transferase T1. Besides, all analogs which could be incorporated in vitro into O-glycans were also integrated into cellular O-glycans as attested by their detectetion on the cell surface of CHO-ldlD cells. Altogether our results show that GalNAc analogs can help to better define structural requirements of the donor substrates for the enzymes involved in GalNAc metabolism and those that are incorporated into cells will prove valuable for the development of novel diagnostic and therapeutic tools.
GalNAc is the initial sugar of mucin-type O-glycans, and is a component of several tumor antigens. The aim of this work was to determine whether synthetic GalNAc analogs could be taken up from the medium and incorporated into complex cellular O-glycans. The cell line employed was CHO ldlD, which can only use GalNAc and Gal present in the medium for the synthesis of its glycans. All GalNAc analogs with modified N-acyl groups (N-formyl, N-propionyl, N-glycolyl, N-azidoacetyl, N-bromoacetyl, and N-chloroacetyl) were incorporated into cellular O-glycans, although to different extents. The GalNAc analogs linked to Ser or Thr could be extended by the β3-galactosyltransferase glycoprotein-N-acetylgalactosamine 3β-galactosyl transferase 1 in vitro and in vivo and by α6-sialyltransferase α-N-acetylgalactosaminide-α-2,6-sialyltransferase 1. At the surface of CHO ldlD cells, all analogs were incorporated into sialylated O-glycan structures like those present on wild-type CHO cells, indicating that the GalNAc analogs do not change the overall structure of core-1 O-glycans. In addition, this study shows that the unnatural synthetic GalNAc analogs can be incorporated into human tumor cells, and that a tumor antigen modified by an analog can be readily detected by a specific antiserum. GalNAc analogs are therefore potential targets for tumor immunotherapy.
