Biological properties of synthetic glycoconjugate mimics of heparin comprising different molecular spacers.

The in vitro antithrombotic activity of synthetic glycoconjugates I and II, comprising a flexible polyethylene glycol type and a rigid polyglucose type spacer, respectively, are compared to heparin.

Feasible synthesis and biological properties of six 'non-glycosamino' glycan analogues of the antithrombin III binding heparin pentasaccharide.

In this paper, we report the synthesis of 'non-glycosamino' glycan analogues 5-10 of the antithrombin III binding pentasaccharide 1. Pentasaccharides 5-10 feature a pseudo-alternating EFGH tetrasaccharide sequence, that is, the disaccharide fragments EF and GH have the same substitution pattern. In the synthetic strategy applied for the synthesis of pentasaccharides 5-10, the properly protected EF disaccharide fragments 19 and 20 are obtained from their GH counterparts 17 and 18 by base-catalyzed epimerization. Series I, comprising pentasaccharides 5-7, has an invariable EFGH tetrasaccharide containing 2-O-sulfate 3-O-methyl uronic acid moieties. Series II, on the other hand, contains pentasaccharides 8-10 and has an invariable EFGH tetrasaccharide containing 2,3-di-O-methyl uronic acid moieties. Coupling disaccharides 17 with 25 and 18 with 26 exclusively afforded the alpha-coupled tetrasaccharides 27 and 28, respectively. Glycosylation of acceptor tetrasaccharides 29 and 30 with glucosyl donors 35, 36 and 39 provided, after deprotection and sulfation, the title-compounds 5-10. Biological data obtained with series I and II indicate that the in vivo half-life but not the intrinsic anti-Xa activity depends on the substitution pattern of the D-unit. In addition, the applicability of reversed UV capillary electrophoresis as an analytical tool to determine the purity of these 'non-glycosamino' glycans is demonstrated.