Base-modified UDP-sugars reduce cell surface levels of P-selectin glycoprotein 1 (PSGL-1) on IL-1β-stimulated human monocytes.

P-selectin glycoprotein ligand-1 (PSGL-1, CD162) is a cell-surface glycoprotein that is expressed, either constitutively or inducibly, on all myeloid and lymphoid cell lineages. PSGL-1 is implicated in cell-cell interactions between platelets, leukocytes and endothelial cells, and a key mediator of inflammatory cell recruitment and transmigration into tissues. Here, we have investigated the effects of the β-1,4-galactosyltransferase inhibitor 5-(5-formylthien-2-yl) UDP-Gal (5-FT UDP-Gal, compound 1: ) and two close derivatives on the cell surface levels of PSGL-1 on human peripheral blood mononuclear cells (hPBMCs).

β-(1→3)-Glucan-mannitol conjugates: scope and amazing results.

It is well known that β-(1→3)-Glucans present high applicative potential in human health as immunostimulating agents. Numerous studies have highlighted this, but mainly used native polysaccharides extracted from various natural sources. These compounds are therefore inevitably polydisperse but also present structures that are not homogeneous, in an analytical point of view.

Linear synthesis of the branched pentasaccharide repeats of O-antigens from Shigella flexneri 1a and 1b demonstrating the major steric hindrance associated with type-specific glucosylation.

Shigella flexneri serotypes 1b and 1a are Gram-negative enteroinvasive bacteria causing shigellosis in humans. The O-antigen from S. flexneri 1b is a { → 2)-[3Ac/4Ac]-α-L-RHAP-(1 → 2)-α-L-Rhap-(1 → 3)-[2Ac]-α-L-Rhap-(1 → 3)-[α-D-Glcp-(1 → 4)]-β-D-GlcpNAc-(1 → }n branched polysaccharide ({(Ac)AB(Ac)C(E)D}n).

Characterization of glycosaminoglycan (GAG) sulfatases from the human gut symbiont Bacteroides thetaiotaomicron reveals the first GAG-specific bacterial endosulfatase.

Despite the importance of the microbiota in human physiology, the molecular bases that govern the interactions between these commensal bacteria and their host remain poorly understood. We recently reported that sulfatases play a key role in the adaptation of a major human commensal bacterium, Bacteroides thetaiotaomicron, to its host (Benjdia, A., Martens, E.

Applying pairwise combinations of amino acid mutations for sorting out highly efficient glucosylation tools for chemo-enzymatic synthesis of bacterial oligosaccharides.

Iterative saturation mutagenesis and combinatorial active site saturation focused on vicinal amino acids were used to alter the acceptor specificity of amylosucrase from Neisseria polysaccharea , a sucrose-utilizing α-transglucosidase, and sort out improved variants. From the screening of three semirational sublibraries accounting in total for 20,000 variants, we report here the isolation of three double mutants of N. polysaccharea amylosucrase displaying a spectacular specificity enhancement toward both sucrose, the donor substrate, and the allyl 2-acetamido-2-deoxy-α-D-glucopyranoside acceptor as compared to the wild-type enzyme.

Inhibition of galactosyltransferases by a novel class of donor analogues.

Galactosyltransferases (GalT) are important molecular targets in a range of therapeutic areas, including infection, inflammation, and cancer. GalT inhibitors are therefore sought after as potential lead compounds for drug discovery. We have recently discovered a new class of GalT inhibitors with a novel mode of action.

New 4-deoxy-(1→3)-β-D-glucan-based oligosaccharides and their immunostimulating potential.

(1→3)-β-D-Glucans are well-established natural biological immunomodulators. However, problems inherited with the natural origin of these polysaccharides bring about significant setbacks, including batch-to-batch heterogeneity and significant differences based on the source and isolation techniques. In this study, we tried to overcome these problems by preparation of a quantitatively new set of oligo-(1→3)-β-D-glucan-based synthetic immunomodulators.

The first C-glycosidic analogue of a novel galactosyltransferase inhibitor.

Structural analogues and mimics of the natural sugar-nucleotide UDP-galactose (UDP-Gal) are sought after as chemical tools for glycobiology and drug discovery. We have recently developed a novel class of galactosyltransferase (GalT) inhibitors derived from UDP-Gal, bearing an additional substituent at the 5-position of the uracil base. Herein we report the first C-glycosidic derivative of this new class of GalT inhibitors.

Biological properties of (1 → 3)-β-D-glucan-based synthetic oligosaccharides.

Despite the fact that β-glucans are well-established immunomodulators, the problems with batch-to-batch heterogeneity remains problematic. The aim of this study was to prepare and evaluate new type of synthetic oligosaccharides. A new family of oligo-(1 → 3)-β-d-glucans modified on the reducing end was synthesized using a controlled and specific inversion of configuration at C-2 starting from already formed oligo-(1 → 3)-β-d-glucans.

Double diastereoselection explains limitations in synthesizing mannose-containing beta-(1,3)-glucans.

It is known that 3-O-glycosylation of glucosidic acceptors bearing acyl groups in the 4 and 6 positions instead of a 4,6-O-benzylidene ring mainly affords alpha-glycosides. Described here is an unexpected stereochemical outcome for elongation at glucose O-3 of a beta-d-Glcp-(1-->3)-alpha-d-Manp disaccharide using peracetylated ethyl thioglucoside as a donor. This unexpected reaction was correlated with match-mismatch effects, as shown by efficient coupling of the same acceptor by a donor of l-configuration.

New oligo-beta-(1,3)-glucan derivatives as immunostimulating agents.

Oligo-beta-(1,3)-glucans were chemically modified in order to introduce a structural variation specifically on the reducing end of the oligomers. The impact of well defined structural modulations was further studied on cancer cells and murin models to evaluate their cytotoxicity and immunostimulating potential.

Design of alpha-transglucosidases of controlled specificity for programmed chemoenzymatic synthesis of antigenic oligosaccharides.

Combined with chemical synthesis, the use of biocatalysts holds great potential to open the way to novel molecular diversity. We report in vitro chemoenzymatic pathways that, for the first time, take advantage of enzyme engineering to produce complex microbial cell-surface oligosaccharides and circumvent the chemical boundaries of glycochemistry. Glycoenzymes were designed to act on nonnatural conveniently protected substrates to produce intermediates compatible with a programmed chemical elongation.

Recent progress in the field of beta-(1,3)-glucans and new applications.

Beta-(1,3)-glucans are widely distributed within microorganisms or seaweeds in which they act as membrane components or for energy storage, respectively. Since these glucans are not biosynthesized by mammals, they are likely to activate the immune system of their host. Since the discovery of their positive involvement as immunomodulator agents, numerous studies were published all around the glycosciences.