Glycobiology Advance Access originally published online on December 8, 2004
Glycobiology 2005 15(4):393-407; doi:10.1093/glycob/cwi020
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Glycobiology vol. 15 no. 4 © Oxford University Press 2004; all rights reserved.
Glucan-like synthetic oligosaccharides: iterative synthesis of linear oligo-ß-(1,3)-glucans and immunostimulatory effects
2 Laboratoire Goëmar, ZAC La Madeleine, Avenue du Général Patton, 35400 Saint Malo, France; 3 Synthèses et Activations de Biomolécules, UMR CNRS 6052, Ecole Nationale Supérieure de Chimie de Rennes, Avenue du Général Leclerc, F-35700 Rennes, France; and 4 Department of Pathology, University of Louisville, 511 S. Floyd Street, MDR Building, Louisville, KY 40202
1 To whom correspondence should be addressed; e-mail: vetvickavaclav{at}netscape.net
Received on September 21, 2004; revised on November 30, 2004; accepted on December 2, 2004
Small reducing and linear oligo-ß-(1,3)-glucans, which are able to act as phytoallexin elicitors or as immunostimulating agents in anticancer therapy, were synthesized according to an iterative strategy that involved a unique key monosaccharidic donor. To avoid anomeric mixtures, the reducing entity of the target oligomers was first locked with benzyl alcohol and further selective deprotection of the 3-OH with DDQ afforded the desired building block as an acceptor. The latter was then used in a second cycle of glycosylation/deprotection to afford the desired disaccharide, and successive reiterations of this process provided the desired oligomers. Unusual conformational behaviors were observed by standard NMR sequences and supported by NOESY studies. Finally, removal of protecting groups afforded free tri-, tetra-, and pentaglucosides in good overall yields. Two oligosaccharides representing linear laminaritetraose and laminaripentaose were compared to the recently described ß-(1,3)-glucan phycarine. Following an intraperitoneal injection, the influx of monocytes and granulocytes into the blood and macrophages into the peritoneal cavity was comparable to that caused by phycarine. Similarly, both oligosaccharides stimulated phagocytic activity of granulocytes and macrophages. Using ELISA, we also demonstrated a significant stimulation of secretion of IL-1ß. Together these results suggest that the synthetic oligosaccharides have similar stimulatory effects as natural ß-(1,3)-glucans.
Key words: carbohydrates / glycosides / glycosylation / immunostimulation / oligosaccharides