Laurent Legentil

Molecular Interactions of β-(1→3)-Glucans with Their Receptors

β-(1→3)-Glucans can be found as structural polysaccharides in cereals, in algae or as exo-polysaccharides secreted on the surfaces of mushrooms or fungi. Research has now established that β-(1→3)-glucans can trigger different immune responses and act as efficient immunostimulating agents. They constitute prevalent sources of carbons for microorganisms after subsequent recognition by digesting enzymes. Nevertheless, mechanisms associated with both roles are not yet clearly understood. This review focuses on the variety of elucidated molecular interactions that involve these natural or synthetic polysaccharides and their receptors, i.e., Dectin-1, CR3, glycolipids, langerin and carbohydrate-binding modules.

Synthesis and antitumor evaluation of analogues of the marine pyrroloiminoquinone tsitsikammamines.

Two series of analogues of the marine pyrroloiminoquinone alkaloids tsitsikammamine have been synthesized on the basis of a Michael addition between 2-amino-1-(4-methoxyphenyl)-ethanol and two indolediones. All the compounds were evaluated in vitro for antiproliferative activity against distinct cancer cell lines.

Oligo-β-(1 → 3)-glucans: impact of thio-bridges on immunostimulating activities and the development of cancer stem cells.

Recent developments of innovative anticancer therapies are based on compounds likely to stimulate the immune defense of the patients. β-(1 → 3)-Glucans are natural polysaccharides well-known for their immunostimulating properties. We report here on the synthesis of small oligo-β-(1 → 3)-glucans characterized by thioglycosidic linkages. The presence of sulfur atom(s) was not only crucial to prolong in vivo immunoactive activities in time, compared to native polysaccharides, but sulfur atoms also had a direct impact on the development of colorectal cancer stem cells. As a result, a short, pure, and structurally well-defined trisaccharidic thioglucan demonstrated similar activities compared to those of natural laminarin.

Identification of Three Elicitins and a Galactan-Based Complex Polysaccharide from a Concentrated Culture Filtrate of Phytophthora infestans Efficient against Pectobacterium atrosepticum

The induction of plant immunity by Pathogen Associated Molecular Patterns (PAMPs) constitutes a powerful strategy for crop protection. PAMPs indeed induce general defense responses in plants and thus increase plant resistance to pathogens. Phytophthora infestans culture filtrates (CCFs) are known to induce defense responses and decrease the severity of soft rot due to Pectobacterium atrosepticum in potato tubers. The aim of this study was to identify and characterize the active compounds from P. infestans filtrate. The filtrate was fractionated by gel filtration, and the protection effects against P. atrosepticum and the ability to induce PAL activity were tested for each fraction. The fraction active in protection (F1) also induced PAL activity, as did the whole filtrate. Three elicitins (INF1, INF4 and INF5) were identified in F1b, subfraction of F1, by MALDI-TOF-MS and MS/MS analyses. However, deproteinized F1b still showed biological activity against the bacterium, revealing the presence of an additional active compound. GC-MS analyses of the deproteinized fraction highlighted the presence of a galactan-based complex polysaccharide. These experiments demonstrate that the biological activity of the CCF against P. atrosepticum results from a combined action of three elicitins and a complex polysaccharide, probably through the activation of general defense responses.

Chapter 19:How recent knowledge on furano-specific enzymes has renewed interest for the synthesis of glycofuranosyl-containing conjugates

d-Galactose in its furanose form is undoubtedly an enigma in glycosciences that has triggered numerous chemical, physical and biological studies over the last thirty years. This chapter is dedicated to show how chemists have been inspired by enzymes involved in the biosynthesis and metabolism of furanosyl-containing conjugates. The resulting molecular tools have proven to be essential for better understanding mutases, furanosyl transferases and furanosyl hydrolases, their impact, their activity and the corresponding biochemical pathways. Moreover, this chapter includes some examples highlighting the use of modern NMR techniques and of molecular biology as new tools in chemical laboratories that contributed to the elucidation of mechanism pathways and/or to the production of new biocatalysts useful for the synthesis of furanosyl-containing conjugates.

Regioselective glycosylation: What's new?

The aim of this chapter is to show how increased understanding of the mechanisms related to both carbohydrate-processing enzymes and intrinsic properties of monoglycosyl residue have significantly impacted our way of thinking about the glycosylation reaction. A focus is made on the importance of low energy interactions. Some recent examples related to biocatalytic approaches and chemical synthesis are given.