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The adhesion of bacteria to human glycoconjugates can be inhibited by soluble glycomimetics that compete with the natural target. Four monovalent and one divalent alpha-fucosyl amides have been tested for their affinity for a fucose-binding lectin from Pseudomonas aeruginosa. Isothermal calorimetric titrations demonstrated that they bind to the lectin in the micromolar range, with highest affinity for the divalent ligand. Molecular modelling established that, compared to Omicron-fucoside compounds, the glycomimetic amide group resulted in the loss of water-bridged hydrogen bonds that could be partially compensated by additional contact of the aglycone with the protein surface.

Molecular dynamics simulations have been performed on fully solvated alpha-(1-->4)-galactosyltransferase LgtC from Neisseria meningitidis with and without the donor substrate UDP-Gal and in the presence of the manganese ion. The analysis of the trajectories revealed a limited movement in the loop X (residues 75-80) and a larger conformational change in the loop Y (residues 246-251) in the simulation, when UDP-Gal was not present. In this case, the loops X and Y open by almost 10A, exposing the active site to the solvent. The 'hinge region' responsible for the opening is composed of residues 246-247. We have also analyzed the behavior of the manganese ion in the simulations. The coordination number is 6 when UDP-Gal is present and it increases to 7 when it is absent. In the latter case, three water molecules become coordinated to the ion. In both cases, the coordination is very stable implying that the manganese ion is tightly bound in the active site of the enzyme even if UDP-Gal is not present. Further analysis of the structural water molecules location confirmed that the mobility of water molecules in the active site and the accessibility of this site for solvent are higher in the absence of the substrate.

Crystals of the disaccharide, (2,3,4,6-tetra- O -acetyl- α - d -glucopyranosyl) (2,3,4,6–tetra- O -acetyl- β - d -glucopyranosyl)amine belong to the space group P2 1 with a =14.848(2), b =21.838(3), c =11.534(2) A, and β =113.72(4)° and Z=4. The crystal structure was solved by direct methods and refined by the full-matrix least squares procedure to an R value of 0.049 ( Rw =0.46) for 4262 observed reflections. This work provides the first crystalline features in the diglycosylamine series and this molecule can be considered as a N -analogue of peracetylated α , β -trehalose. The conformational features of the two independent diglycosylamine molecules do not display any major significant differences. The d –glucopyranose residues have the usual 4 C 1 chair conformations, whereas all the primary and secondary acetate groups display usual orientations. In the crystal structure the hydrogen atom covalently linked to the nitrogen at the glycosidic linkage could be located; its configuration is ( R ) providing the priority is given to the ( R ) carbon neighbor (C-1 β ). The torsional angles at the glycosidic linkages Φα (O-5–C-1 α –N-1–C-1 β ), Φβ (C-1 α –N-1–C-1 β –O-5) of the two molecules have values of (57.6°,−78.8°) and (59.8°,−85.9°), respectively, slightly different from the conformation found in α , β -trehalose monohydrate. These conformations have been rationalized through the use of molecular mechanics calculations. The packing mode is highly anisotropic, with the existence of chains of molecules along the c axis, stabilized by numerous van der Waals contacts and by a strong hydrogen bond, involving the NH group of the glycosidic linkage and the carbonyl group of one acetate.

International audience; Under microwave activation, the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) between an azido-functionalized lactoside and tetra-alkynylated core scaffolds (one porphyrin and three topological conformers of calix[4]arenes) afforded four lactosylated glycoclusters in high yields. The glycoclusters were then evaluated and compared to a monovalent probe as ligands of two lectins: ECA from legume plant Erythrina cristagalli and recombinant human galectin-1. Micromolar inhibition concentrations and IC(50) values were measured by inhibition of hemagglutination (HIA) or enzyme-linked lectin assays (ELLA), respectively for these glycoclusters for binding to ECA. A slight binding preference was identified for the porphyrin and the 1,3-alternate calixarene scaffolds. Similar inhibition studies were performed for galectin-1 by HIA and surface plasmon resonance (SPR) analyses. A strong selectivity was observed for the porphyrin and cone conformer topologies under HIA experimental conditions but these could not be confirmed using SPR analysis. This difference in the inhibitory properties based on two techniques confirmed the need for multiple complementary analyses for in-depth and accurate analysis of the inhibitory properties of multivalent glycoconjugates to multivalent lectins.

The conformational behaviour of methyl β- d - and methyl α- l -arabinofuranosides have been assessed through computations performed with the molecular mechanics program MM3 using the flexible residue method. Energies for various envelope and twist conformers were calculated as a function of the puckering parameters Q and Φ. The gauche-gauche, gauche-trans, and trans-gauche orientations of the primary hydroxyl groups at C-5 were accounted for. Our calculations provide some insight into extensive conformational flexibility that both molecules display and shed light on the possible pathways for conformational interconversions. Both molecules display very characteristic conformational behaviour. The conformations of methyl β- d -arabinofuranoside, which have been determined by single-crystal X-ray diffraction studies, are distributed in two fairly deep low-energy wells. These conformations are no more than 1.5 kcal/mol above the respective energy minima. In the case of methyl α- l -arabinofuranoside, crystallographic data are lacking and only 1 H- 1 H coupling constants are available. Using suitable equations for the H-C-C-H segments, the theoretical 3 J H-H coupling constants were calculated as a function of the two puckering parameters, taking into account all the accessible conformations. Agreement with the experimentally reported data confirms the high flexibility of furanose rings in solution.

The cyclic tetrasaccharide cyclo-[--6)-alpha-D-Glcp-(1--3)-alpha-D-Glcp-(1--6)-alpha-D-Glcp-(1--3)-alpha-D-Glcp-(1--] is the major compound obtained by the action of endo-alternases on the alternan polysaccharide. Crystals of this cyclo-tetra-glucose belong to the orthorhombic space group P2(1)2(1)2(1) with a = 7.620(5), b = 12.450(5) and c = 34.800(5) A. The asymmetric unit contains one tetrasaccharide together with five water molecules. The tetrasaccharide adopts a plate-like overall shape with a very shallow depression on one side. The shape is not fully symmetrical and this is clearly apparent on comparing the (phi, psi) torsion angles of the two alpha-(1--6) linkages. There is almost 10 degrees differences in phi and more than 20 degrees differences in psi. The hydrogen bond network is asymmetric, with a single intramolecular hydrogen bond: O-2 of glucose ring 1 being the donor to O-2 of glucose ring 3. These two hydroxyl groups are located below the ring and their orientation, dictated by this hydrogen bond, makes the floor of the plate. Among the five water molecules, one located above the center of the plate occupies perfectly the shallow depression in the plate shape formed by the tetrasaccharide. Molecular dynamics simulation of the tetrasaccharide in explicit water allows rationalization of the discrepancies observed between the X-ray structures and data obtained previously by NMR.

The solution conformation of two lipooligosaccharides related to Nod factors or lipochitoligosaccharides have been analysed by 1D and 2D 1H and 13C NMR spectroscopy, molecular mechanics and dynamics calculations. The obtained data indicate that the glycosidic torsion angles have restricted fluctuations, but may adopt a variety of shapes. Remarkably, the relative orientation of the fatty acid chain towards the oligosaccharide backbone is solvent dependent. In water solution, the acyl residue and the oligosaccharide adopt a quasi-parallel orientation for a significant amount of time.

The viscous exopolysaccharide (EPS) produced by Lactobacillus sake 0–1 is a high molecular mass polymer ( M m 6 × 10 6 Da) consisting of pentasaccharide repeating units with a composition of d -glucose, l -rhamnose, and sn -glycerol 3-phosphate in molar ratios of 3:2:1. One of the rhamnose residues in the repeating unit is partially 2- O -acetylated. The O -deacetylated, deglycerophosphorylated EPS has been investigated by molecular mechanics calculations. A complete conformational analysis of each of the constituent disaccharide fragments has been performed using the flexible residue approach with the MM3(92) force field. Furthermore, using the same force field, CICADA analyses were accomplished on hexa- and octasaccharide substructures of the polysaccharide. Based on these analyses, insight was obtained into nine conformational minima for the polysaccharide. The low energy conformations found by CICADA were extrapolated to regular polysaccharide structures using a polysaccharide builder program. The generated helices exhibit either 2-fold or 3- or 4-fold righthanded chiralities, and in each case the helices are highly extended.