Effecteurs membranaires : syntheses et structures de phosphates et phosphonates dans la serie des dolichols

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Penser autrement l’alternance en formation au service de l’apprentissage professionnel du sujet « travailleur et apprenant »

Cet article porte sur une formation action réalisée à l’École d’infirmières puéricultrices du CHU de Montpellier dont l’objectif principal est d’élaborer un curriculum de formation selon une construction par situations d’apprentissage professionnel. Penser autrement les dispositifs de formation basés sur l’alternance cours stage et s’interroger sur le sens de la professionnalisation est une opportunité à saisir dans le cadre de la réingénierie des formations en santé. Dans ce contexte, proposer une forme d’alternance dialectique – apprentissage dans et par une activité située et problématisée - est une perspective judicieuse pour la formation des infirmières puéricultrices afin de donner du sens à cette alternance au regard d’une ambition d’apprentissage professionnel.This article focuses on the training/operation course offered at the Nurse and Pediatric Nurse school of Montpellier University Hospital aiming to develop a training program based on a construction of learning through professional situations. Thinking differently the training system based on alternation between course and internship and questioning the meaning of professionalization is an opportunity to be seized in the context of health formations reengineering. In that respect, offering a dialectical-learning alternation in and through a situated and problematized activity is a judicious perspective for Nurses and Pediatric Nurses training in order to give meaning to work-study by giving a real ambition for professional learning

Dimerization of A82846B, vancomycin and ristocetin: Influence on antibiotic complexation with cell wall model peptides

Abstract The thermodynamics of glycopeptide antibiotic dimerization have been studied by means of sedimentation equilibrium, using A82846B, vancomycin, ristocetin and complexes formed with several cell wall model pep tides. These results indicate that vancomycin dimerization can be strongly promoted in two ways: i) stabilization of the antibiotic conformation in which the carbonyl group of residue three is on the back face of the molecule and ii) preferential interaction of the dimer with the lysine residue of N, N'-diacetyl-lysyl-D-alanyl-D-alanine. This effect was not found in ristocetin. A82846B forms stable dimers at very low antibiotic concentration. Two conformational forms have been found for complexed A82846B by 1H NMR. However, calorimetric binding experiments have shown that all its binding sites are thermodynamically equivalent. The affinity of the A82846B dimer for the tripeptide has been estimated to be about SkJ • mol-1 higher than that of the vancomycin monomer and about -2.6kJ•mol-1 lower than that of dimeric vancomycin. The possible role of dimerization in the biological activity of glycopeptide antibiotics1) is discussed further on the basis of present thermodynamic data.This work was supported by Grant PB90-0112 from the Spanish D.G.I.C.Y.T. and H. Linsdell received a fellowship from the M.E.

Three-dimensional structure of the complexes of ribonuclease A with 2',5'-CpA and 3',5'-d(CpA) in aqueous solution, as obtained by NMR and restrained molecular dynamics

The three-dimensional structure of the complexes of ribonuclease A with cytidyl-2′,5′-adenosine (2′,5′-CpA) and deoxycytidyl-3′,5′-deoxyadenosine [3′,5′-d(CpA)] in aqueous solution has been determined by 1H NMR methods in combination with restrained molecular dynamics calculations. Twenty-three intermolecular NOE cross-correlations for the 3′,5′-d(CpA) complex and 19 for the 2′,5′-CpA, together with about 1,000 intramolecular NOEs assigned for each complex, were translated into distance constraints and used in the calculation. No significant changes in the global structure of the enzyme occur upon complex formation. The side chains of His 12, Thr 45, His 119, and the amide backbone group of Phe 120 are involved directly in the binding of the ligands at the active site. The conformation of the two bases is anti in the two complexes, but differs from the crystal structure in the conformation of the two sugar rings in 3′,5′-d(CpA), shown to be in the S-type region, as deduced from an analysis of couplings between the ribose protons. His 119 is found in the two complexes in only one conformation, corresponding to position A in the free protein. Side chains of Asn 67, Gln 69, Asn 71, and Glu 111 form transient hydrogen bonds with the adenine base, showing the existence of a pronounced flexibility of these enzyme side chains at the binding site of the downstream adenine. All other general features on the structures coincide clearly with those observed in the crystal state.This work was supported by the Spanish Direccion General de Investigación Cientifica y Técnica, project n. PB93-0189

A new skeletal triterpenoid isolated from Empetrum nigrum

A new skeletal triterpenoid hydrocarbon, named nigrum-21-en-3-one (1) has been isolated from aerial parts of Empetrum nigrum L. The structure of this compound has been unambiguously established on the basis of 1H- and 13C-two dimensional nuclear magnetic resonance studies

A synthetic receptor for dinucleotides

Complexation of biorelevant targets with synthetic receptors continues to provide information regarding recognition at the molecular level.2 One tactic involves the concatenation of modular subunits with complementarity to specific domains of the target. Here we apply this means to develop a system (receptor 1) for the complexation of 2'-deoxyadenylyl(3,->5')-2,-deoxyadenosine (<f(AA)) and give evidence of its success.We thank the National Institutes of Health for support of this work. We are also indebted to Dr. Ramón Eritja, CSIC, Barcelona, Spain, for a sample of </(AA)

Three-Dimensional Solution Structure and Stability of Thioredoxin m from Spinach †

Proton NMR spectral resonances of thioredoxin m from spinach have been assigned, and its solution structure has been determined on the basis of 1156 nuclear Overhauser effect- (NOE-) derived distance constraints by using restrained molecular dynamics calculations. The average pairwise root-mean-square deviation (RMSD) for the 25 best NMR structures for the backbone was 1.0 +/- 0.1, when the structurally well-defined residues were considered. The N- and C-terminal segments (1-13 and 118-119) and residues 41-49, comprising the active site, are highly disordered. At the time of concluding this work, a crystal structure of this protein was reported, in which thioredoxin m was found to crystallize as noncovalent dimers. Although the solution and crystal structures are very similar, no evidence was found about the existence of dimers in solution, thus confirming that dimerization is not needed for the regulatory activity of thioredoxin m. The spinach thioredoxin m does not unfold by heat in the range 25-85 degrees C, as revealed by thermal circular dichroic (CD) measurements. However, its unfolding free energy (9.1 +/- 0.8 kcal mol(-1), at pH 5.3 and 25 degrees C) could be determined by extrapolating the free energy values obtained at different concentrations of guanidinium chloride (GdmCl). The folding-unfolding process is two-state as indicated by the coincidence of the CD denaturation curves obtained at far and near UV. The H/D exchange behavior of backbone amide protons was analyzed. The slowest-exchanging protons, requiring a global-unfolding mechanism in order to exchange, are those from beta2, beta3, and beta4, the central strands of the beta-sheet, which constitute the main element of the core of the protein. The free energies obtained from exchange measurements of protons belonging to the alpha-helices are lower than those derived from GdmCl denaturation studies, indicating that those protons exchange by local-unfolding mechanisms.Fil: Neira, José L.. Universidad de Miguel Hernández; EspañaFil: González, Carlos. Consejo Superior de Investigaciones Científicas; EspañaFil: Toiron, Catherine. Consejo Superior de Investigaciones Científicas; EspañaFil: de Prat Gay, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rico, Manuel. Consejo Superior de Investigaciones Científicas; Españ

Conformational studies of a short linear peptide corresponding to a major conserved neutralizing epitope of human respiratory syncytial virus fusion glycoprotein

The conformational properties of a 21-residue peptide, corresponding to amino acids 255 to 275 (F255-275) of the human respiratory syncytial virus fusion (F) glycoprotein, have been studied by CD and nmr spectroscopy. This peptide includes residues 262, 268, and 272 of the F polypeptide that are essential for integrity of most epitopes that mapped into a major antigenic site of the F molecule. CD data indicate that F255-275 adopts a random coil conformation in aqueous solution at low peptide concentrations. However, as the concentration of peptide is increased, a higher percentage of peptide molecules adopts an organized structure. This effect can be more easily observed when trifluoroethanol (30%) is added to peptide solutions, giving rise to CD spectra that resemble those of α-helix structures. These conformational changes were confirmed by nmr spectroscopy. The nuclear Overhauser effects observed in 30% trifluoroethanol/water together with the conformational Hα chemical shift data allowed us to propose a structural model of helix-loop-helix for the peptide in solution. In addition, these helical regions contain the amino acid residues essential for epitope integrity in the native F molecule. These results give new insights into the antigenic structure of the respiratory syncytial virus F glycoprotein.This work was supported by grant PB90- 0120 from Comisión Interministerial de Ciencia y Tecnología, by grant PB9 1-0266 from DGICYT (to DA in Barcelona) and by grant SAF94-0045 (to JAM in Madrid)

High-performance liquid-chromatographic determination of the pi-values of azol-N-yl substituents

The π (hydrophobic constant) values for 16 parent azoles (pyrrole, imidazole, pyrazole, four triazoles, two tetrazoles, indole, benzimidazole, 1 H and 2H-indazoles, 1H-and 2H-benzotriazoles, and carbazole) were calculated from the logarithms of the capacity factors (log k′) determined by HPLC. The values thus obtained are discussed according to an additive model in which the number and position of pyridinelike nitrogen atoms and the annelation effect are considered.J. A. B., T. C., and R.L.acknowledge financial support from the Comisión lnterministerial de Ciencia y Tecnología through project. PB87-0755

The tautomerism of 3(5)-phenylpyrazoles: An experimental (1H, 13C, 15N NMR and X-ray crystallography) study

3(5)-Phenyl- and 5(3)-methyl-3(5)-phenylpyrazole have been studied using multinuclear NMR spectroscopy at low temperature to determine the tautomeric equilibrium constants in the slow proton exchange regime by simple signal integration. In order to compare the results in solution with those in the solid state, the X-ray structure of a derivative of the first, namely 4-bromo-3-phenylpyrazole was determined [triclinic, P[1 with combining macron], a= 13.0867(8), b= 13.2546(7), c= 7.8079(3)Å, α= 100.015(4), β= 93.648(3), γ= 84.923(5)°, Z= 6]. The conclusions are that 3(5)-phenylpyrazoles exist in solution as mixtures rich in the 3-phenyl tautomer which is also the tautomer present in the solid state, whereas they form monomers which are hydrogen bonded to the solvent in liquids like THF and self associate in inert solvents.Peer reviewe