Synthesis of Fragment of beta-Glucans as Potential Ligands for Dectin-1

Beta-glucans are glucose polymers linked together by a 1,3 linear beta-glycosidic chain core, differing from each other by their length and branching configuration. The branches derived from the glycosidic chain core are either 1,4 or 1,6 glycosidic chains and appear to be dependent on the source. Dectin-1 is a unique C-type lectin that recognizes beta-glucan carbohydrates present on the surface of various fungi, including C. albicans. Its activation promotes microbial uptake and phagocytosis, but also mediates, in synergy with TLRs, the production of cytokines such as IL-12 and TNF alfa, leading ultimately to the initiation of the adaptive immune response. For this reason, beta-glucans – or their fragments – can be referred to as a possible class of adjuvants to increase the immune response to pathogens. In addition, the administration of beta-glucan-derived compounds can help in gaining new insights on the mechanism of action of dectin-1 receptor. Dectin-1 binds beta-glucan polymers with affinities ranging from very low (3x10-3 M) to very high (2x10-12 M). The wide range of affinities appears to be due to the differing sizes and numbers of branches in -glucans from various sources. Although the interaction between Dectin-1 and beta-glucans has been supposed to involve a conformational epitope as a high order local helix, little is known about the binding mode and the degree of (1-6)-branching of the glucan chain in the binding epitope. For this reason, a series of fragments of beta-glucans, differing in the 6-O branching degree, has been synthesised. Their ability to bind to dectin-1 and of activating the inflammatory response will be subsequently tested.