Development of new functional glycans and the applications

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We have examined the molecular requirements of selectin recognition by use of a variety of synthetic carbohydrate analogues with specific modifications on the sialyl-Lewis X,a binding epitope of leukocyte-endothelial cell adhesion molecules (selectins). E- and L-Selectins require OH groups at c-2,3 and 4 of the L-fucose moiety, while p-selectin requires only oh-3. Modifications of the sialic acid moiety, except for the carboxyl group, have little effect on the binding of any of the selectins. All three selectins-bound efficiently to an sulpho-Lewis X analogue in which sialic acid and ceramide are replaced with the sulfate group and an artificial long-chain alkyl (B-30) , respectively. This molecule is now being examined for biomedical applications as an anti-inflammatory as well as anti-metastatic agent.It is of interest that a synthetic 2- (tetradecyl) hexadecyl 0- (5-acetamido-3,5-didoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonic acid) - (2-3) -0-beta-D-galactopyranosyl- (1-4) -beta-D-glucopyranoside, an analogue of ganglioside GM3, markedly inhibited the cellular immune response. This effect was quantitatively similar to that of cyclosporin A.