Karine Descroix

Recent Progress in the Field of β-(1,3)-Glucans and New Applications

β-(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. These works deal with purification procedures, analytical chemistry, synthetic processes, chemical modification of the natural polysaccharides, determination of their physicochemical properties, and assessment of their biological and medicinal effects through in vitro and in vivo studies. This article aims at presenting some recent results linked to β-(1,3)-glucans through two closely connected points of view, i.e. biology and chemistry. Biological aspects will be focused more particularly on discovery of some receptors present on immunocompetent cells and scope and limitations of chemical synthesis and/or modifications will be described. Moreover, this paper will also introduce some new chemo-enzymatic synthetic methods using wild-type or mutant glycosidases and will be extended to novel opportunities of applications of β-(1,3)-glucans in nanotechnology resulting from a better understanding of their self-assembling propensity in aqueous media.

New oligo-β-(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.

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. Some of these non-natural oligosaccharides showed biological activities, such as stimulation of phagocytosis, modulation of gene expression, and anti-cancer activity, which were superior to natural glucans.

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. The designed glycosides are characterized by the presence of four or five glucopyranose entities and a mannose residue at the reducing end. To study of the impact of well-defined structural modulations, we used murine and human models to evaluate their immunostimulating potential. These novel oligosaccharides showed strong and long-lasting stimulation of phagocytosis and significant potentiation of synthesis and/or secretion of interleukin (IL-2, IL-4, IL-5, IL-6), tumor necrosis factor-α, and vascular endothelial growth factor. In addition, the oligosaccharides tested showed significant effects on expression of several genes in human fibroblasts and breast cancer cells. From our results it is clear that these synthetic oligosaccharides represent a better alternative to natural β-glucans.

Double diastereoselection explains limitations in synthesizing mannose-containing β-(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.

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. This is the reason why we have achieved the chemical synthesis of small glucan-mannitol derivatives especially found in brown seaweeds. The targets differ from each other by the nature of the conjunction between the laminaribiose and the mannose or mannitol, i.e., (1→6) or (1→3). We established that (I) these molecules were efficiently obtained from glucose, laminaribiose and/or mannose derivatives; (II) the synthetic plan has to be adapted to the first connection between a glucosyl entity and the mannosyl residue; and (III) resulting pure compounds may be used as the standard for analytical purposes.