In this study, biologically active oligosaccharides were synthesized based on one-pot glycosylation. One-pot glycosylation enables direct coupling of multi-saccharide building blocks via sequential chemo- and regio-selective glycosylations in a single vessel. A di-branched heptasaccharide was synthesized by one-pot glycosylation using seven independent building blocks. The glycosyl amino acids containing sialic acids were covered by the one-pot glycosylation, in which sialylation was achieved with N-Troc-protected thiosialoside. Combinatorial oligosaccharide libraries were synthesized by one-pot glycosylation using parallel and automated synthesizers. This study also developed a polymer-assisted strategy for deprotection of protected oligosaccharides.
Fungal cell wall polysaccharides serve as target molecules for phagocytes, including macrophages, and neutrophils. These polysaccharides are specifically recognized by C-type lectins on the leukocytes. Dectin-1, a glycoprotein C-type lectin receptor for 1,3-β-glucans, is assumed to be involved in recognizing pathogenic fungi such as Candida albicans. However, the physiological role of Dectin-1 in innate immunity activation during the initial host defense and in some inflammatory diseases remains unclear. Therefore, it is crucial to investigate the contribution of this receptor to the immune system. By using Dectin-1-knockout mice and specific antibodies, we investigated the mechanisms by which Dectin-1 recognizes 1,3-β-glucan and activates innate and tumor immunity. Dectin-1 interacts with 1,3-β-glucosyl chains through a mechanism distinct from other C-type lectins. Dectin-1 activates NF-κB through cooperation with TLR2-mediated signaling and through the CARD9-mediated pathway independent of TLRs. NF-κB activation by Dectin-1 requires Trp-Ile-His sequence on the carbohydrate recognition domain and the cytoplasmic ITAM motif. In vivo study using Dectin-1-knockout mice and neutralizing antibodies revealed the crucial role of Dectin-1 in host defense against fungal infection and in antitumor activity modulated by β-glucan administration. In conclusion, Dectin-1 is an indispensable receptor for recognizing 1,3-β-glucans and for activating host immune systems against fungal invasion.
GlycoWord, an internet site that had been run in collaboration with FCCA and Seikagaku Corporation since December of 1997, decided to stop releasing a new issue at the end of 2006. GlycoWord is the first glossary of keywords used in glycoscience fields, and explains these words concisely and precisely in both Japanese and English. GlycoWord has been frequently used by many people not only in Japan but also throughout the world. Ten years have passed since its first release and GlycoWord appears to have ended its role during the developing period of glycosciences. Now, comes a turning point at which we should be looking for a new role for GlycoWord toward an expanding stage of glycosciences.