705 research outputs found
Advancing public health: enabling culture-fair and education-independent automated cognitive assessment in low- and middle-income countries
No full textCITATION Garuma D, Lamba D, Abessa TG and Bonnechère B () Advancing public health: enabling culture-fair and education-independent automated cognitive assessment in low-and middle-income countries.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the NASCERE program
Structure analysis of methyl a-L-fucopiranoside by X-ray crystallography, NMR spectroscopy and molecular mechanics calculations
No full textPurification, crystallization, X-ray diffraction analysis and phasing of a Fab fragment of monoclonal neuroantibody alphaD11 against nerve growth factor
No full textThe rat monoclonal neuroantibody alphaD11 is a potent antagonist that prevents the binding of nerve growth factor (NGF) to its tyrosine kinase A receptor (TrkA) in a variety of systems, most notably in two in vivo systems linked to crucial pathological states, such as Alzheimer's disease and HIV infection. To provide further insights into the mechanism of action of this potentially therapeutic monoclonal antibody, structural studies of the antigen-binding fragment (Fab) of alphaD11 were performed. alphaD11 IgG2a immunoglobulin was obtained from hybridomas by in vitro tissue culture. The alphaD11 Fab crystallizes in two crystal forms. Form I belongs to space group P1, with unit-cell parameters a = 42.7, b = 50.6, c = 102.7 A, alpha = 82.0, beta = 89.1, gamma = 86.0 degrees. With two molecules in the asymmetric unit, V(M) is 2.3 A(3) Da(-1) and the solvent content is 46%. A complete data set has been collected at 2.7 A resolution on beamline XRD-1 (ELETTRA, Trieste, Italy). Form II belongs to space group C2, with unit-cell parameters a = 114.8, b = 69.4, c = 64.10 A, beta = 117.0 degrees. With one molecule in the asymmetric unit, V(M) is 2.4 A(3) Da(-1) and the solvent content is 48%. A complete data set has been collected at 1.7 A resolution on beamline ID14-1 (ESRF, Grenoble, France). Phasing was successfully performed by Patterson search techniques and refinement of the structures is currently under way. Crystal forms I and II display a close-packing pattern
Absolute-configuration of Seiricuprolide, A New Phytotoxin From Seiridium-cupressi
No full textC14H20O5, M(r) = 268.31, monoclinic, P2(1), a = 5.0680 (5), b = 19.519 (2), c = 7.3968 (8) angstrom, beta = 106.03 (1)-degrees, V = 703.3 (1) angstrom 3, Z = 2, D(x) = 1.27 g cm-3, lambda(Cu K-alpha) = 1.54184 angstrom, mu = 7.55 cm-1, F(000) = 288, T = 298 K, R = 0.029 for 1286 reflections with F(o) greater-than-or-equal-to 4-sigma(F(o)). The absolute configurations of C4, C5, C6, C7 and C13 are R, S, R, S and S respectively. The C1-C2 and C8-C9 double bonds have E and Z configurations respectively. The determination of the absolute configuration of the title compound also allows that of its trans-bromohydrin derivative to be established
Neutralization of NGF-TrkA receptor interaction by the novel antagonistic anti-TrkA monoclonal antibody MNAC13: A structural insight
No full textMNAC13, a mouse monoclonal antibody, recognizes with high affinity and specificity the neurotrophin receptor TrkA and displays a neutralizing activity toward the NGF/TrkA interaction. Detailed knowledge of the molecular basis determining the specificity of this antibody is of importance because of its potential use as a modulator of the TrkA-mediated NGF activity. Here, we report a full biochemical and structural characterization of the MNAC13 antibody. Epitope mapping studies, by serial deletion mutants and by phage display, reveal a conformational epitope that is localized on the carboxy-terminal region of the first immunoglobulin-like domain (d4) of TrkA. The X-ray crystal structure of the MNAC13 Fab fragment has been determined and refined to 1.8 A resolution. The antigen-binding site is characterized by a crevice, surrounded by hydrophilic-charged residues on either side, dipping deep toward three mainly hydrophobic subsites. Remarkably an isopropanol molecule has been found to bind in one of the hydrophobic crevices. Overall, the surface topology (shape and electrostatic potential) of the combining site is consistent with the binding data on TrkA ECD serial deletions mutants. The structure of the MNAC13 Fab fragment may assist in the rational structure-based design of high affinity humanized forms of MNAC13, appropriate for therapeutic approaches in neuropathy and inflammatory pain states
SYNTHESIS OF 2,3-4,6-DI-O-ISOPROPYLIDENE DERIVATIVES OF ALKYL-ALPHA-GALACTOPYRANOSIDES AND ALKYL-BETA-D-GALACTOPYRANOSIDES, AND ELUCIDATION OF STRUCTURE BY NMR AND X-RAY-ANALYSIS
No full textKinetically controlled reaction of 4.5 equiv. of 2-methoxypropene with some alkyl α- and β-d-galactopyranosides gave the 2,3:4,6-di-O-isopropylidene derivatives in high yields (80-85%). With 2 equiv. of 2-methoxypropene, benzyl β-d-galactopyranoside gave the 4,6- and the 3,4-monoacetals in the ratio 30:1 together with ∼20% of the 2,3:4,6-diacetal. The structures of methyl 2,3:4,6-di-O-isopropylidene-α- and -β-d-galactopyranosides were determined by X-ray analysis. The former crystallised in the orthorhombic system, P212121, with a = 5.503, b = 16.105, c = 16.822 Å, and Z = 4, the latter in the monoclinic system, P21, with a = 10.400, b = 13.344, c = 11.647 Å, β = 111.50, and Z = 4. The α anomer and the two molecules of the β anomer had the d-galactopyranoside and the 1,3-dioxane rings in twist-chair conformations and the dioxolane ring in a half-chair conformation. N.m.r. spectroscopy suggested the occurrence of similar conformations in solution
Purification, crystallization and preliminary X-ray analysis of the Fab fragment from MNAC13, a novel antagonistic anti-tyrosine kinase A receptor monoclonal antibody.
No full textThe monoclonal antibody MNAC13 is a potent antagonist that prevents the binding of nerve-growth factor (NGF) to its tyrosine kinase A receptor (TrkA) in a variety of systems. Structural studies of the FabMNAC13 fragment were performed to gain insights into the mechanism of action of this potentially therapeutic monoclonal antibody. The optimal conditions for crystallization of FabMNAC13 were determined. Crystals appeared as prismatic bundles, displayed P2(1)2(1)2(1) space-group symmetry and diffracted to a resolution of 1.8 A. The unit-cell parameters were determined to be a = 52.73, b = 67.55, c = 111.43 A. The data set was 99.5% complete. Molecular replacement was performed, resulting in a correlation coefficient of 0.55 and an R value of 0.40. The structure refinement is now in progress
- …
