A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics

The vascular endothelial growth factor (VEGF) family of cytokines plays a key role in vasculogenesis, angiogenesis, and lymphangiogenesis. VEGF-A is the main member of this family, alongside placental growth factor (PlGF), VEGF-B/C/D in mammals, and VEGF-E/F in other organisms. To study the activities of these growth factors under physiological and pathological conditions, resulting in therapeutic applications in cancer and age-related macular degeneration, blocking ligands have been developed. These have mostly been large biomolecules like antibodies. Ligands with high affinities, at least in the nanomolar range, and accurate structural data from X-ray crystallography and NMR spectroscopy have been described. They constitute the main focus of this overview, which evidences similarities and differences in their binding modes. For VEGF-A ligands, and to a limited extent also for PlGF, a transition is now observed towards developing smaller ligands like nanobodies and peptides. These include unnatural amino acids and chemical modifications for designed and improved properties, such as serum stability and greater affinity. However, this review also highlights the scarcity of such small molecular entities and the striking lack of small organic molecule ligands. It also shows the gap between the rather large array of ligands targeting VEGF-A and the general absence of ligands binding other VEGF members, besides some antibodies. Future developments in these directions are expected in the upcoming years, and the study of these growth factors and their promising therapeutic applications will be welcomed

The 2.2 Å resolution structure of thermolysin (TLN) crystallized in the presence of potassium thiocyanate

International audienceA new crystallization protocol for thermolysin (EC 3.4.24.27) from Bacillus thermoproteolyticus is presented. After dissolving the protein in the presence of KSCN, which avoids the use of DMSO and CsCl, crystals were obtained following the salting-in method. Crystal cell parameters are isomorphous with those previously reported from DMSO/CsCl mixtures. The new SCN crystal structure has been analyzed. It shows the presence of one thiocyanate ion in the catalytic site and several rearrangements in the S 1 and S 2 subsites. These results are in agreement with the measurements of Inouye et al. [(1998), J. Biochem. (Tokyo), 123, 847±852], who observed in solution that the solubility of TLN, which is particularly poor in low ionic strength solutions, increases dramatically in the presence of several neutral salts. The results reported here suggest possible explanations for the solubility increase and for the inhibitory effects of high SCN concentrations on thermolysin activity

Dynamique fluviale et anthropisation d'un fond de vallée : l'exemple de l'auto-capture du Rhône dans la plaine des Basses Terres dauphinoises (Ain, Isère, France)

International audienc

La gestion des eaux en fond de vallée à l'époque romaine dans l'avant pays alpin : les bassin s rhodaniens des Basses Terres et de Malville

International audienc

La gestion des eaux en fond de vallée à l'époque romaine dans l'avant pays alpin : les bassin s rhodaniens des Basses Terres et de Malville

International audienc

Pour une histoire de l''hydraulique agricole : Méthodologie et études de cas (France, Etats-Unis)

International audienc

Experimental Measurement of CO2 Solubility in Aqueous NaCl Solution at Temperature from 323.15 to 423.15 K and Pressure of up to 20 MPa

ACLInternational audienceInterest in CO2 solubility in brine at high pressure and high temperature has grown in the last few decades. Solubility data are especially important in petroleum geology, carbon capture and geological storage, and geothermal reservoir engineering. Nevertheless, for the CO2 + NaCl + H2O system there are fewer solubility data available in literature, particularly at high salt molality. A high-pressure experimental device was designed to perform measurements for carbon dioxide solubility in a complex aqueous solution. The apparatus was first validated from experiment on the CO2-pure water system at 323.15 K by comparison with literature data. Thirty-six new experimental solubility data point were obtained in the pressure range between 5 and 20 MPa at three temperatures (323.15, 373.15, and 423.15 K) and at three molalities of NaCl (1, 3, and 6 moles per kilogram of water). Solubility measurements were obtained by potentiometric titration after sample trapping in a sodium hydroxide solution. The experimental solubility data generated in this work were consistent with literature data, and four original isotherms were obtained at high salinity. \textcopyright 2016 American Chemical Society

Review: Behaviour of endothelial cells face to hypoxia

International audienc

Experimental Measurement of CO2 Solubility in Aqueous CaCl2 Solution at Temperature from 323.15 to 423.15 K and Pressure up to 20 MPa Using the Conductometric Titration

ACLInternational audienceIn the framework of the efforts of the scientific community developed for the reduction of CO2 emissions, the geological storage of CO2 in deep saline aquifers is under focus. An increase of salinity decreases the potential of CO2 solubilization into the water. In salty waters, the salinity is not only due to NaCl but also to others ions and in particular Ca and Mg. Experimental solubility data of CO2 in calcium chloride solution available in the literature at conditions relevant to carbon storage are particularly scarce. In this work, a new analytical method was developed for experimental measurement of CO2 solubility in calcium chloride solutions (1, 3, and 6 mol/kg) at high pressures (5-20 MPa) and temperatures (323.15, 373.15, and 423.15 K). This method is based on conductometric titration coupled with classical pH titration. The conductimetry shows sharper curves than the pH titration allowing a higher precision. Thirty-six new experimental data are reported in this paper. These data presented an experimental average uncertainty of 2.1% with the ANOVA calculation method based on repeatability and reproducibility experiments. The CO2 solubility in CaCl2 solutions is noticeable lower than in NaCl solution increasing the salting out effect. Considering our previous work on NaCl solutions and this paper for CaCl2 solutions, estimations of the real quantity of CO2 that may be dissolved in saline aquifers can be made with a significantly better precision

Pour une histoire de l’hydraulique agricole, méthodologie et étude de cas (France, etats-Unis)

National audiencePour une histoire de l’hydraulique agricole, méthodologie et étude de cas (France, etats-Unis