Synthesis and anticoagulation studies of "short-armed" fucosylated chondroitin sulfate glycoclusters

Abstract

Fucosylated chondroitin sulfate (FuCS) is a structurally complex glycosaminoglycan found in sea cucumbers with a wide spectrum of biological activities, among which anticoagulant activity is particularly attractive for the development of alternative anticoagulant drugs with decreased adverse effects and risks of bleeding. Previous studies show that FuCS glycomimetics bearing several trisaccharide epitopes displayed promising anticoagulant activity and did not change the mode of action of FuCS. To simplify synthetic difficulty of high valent glycoclusters and obtain candidate compounds with relatively low molecular weights, here we report the synthesis of two FuCS glycoclusters with low valence and more compact structures. Anticoagulation studies showed that these simplified "short-armed" glycoclusters demonstrated comparable potency with "long-armed" high valent glycoclusters, offering a concise approach for the development of novel anticoagulant agents.

Keywords: Anticoagulant; Carbohydrate; Fucosylated chondroitin sulfate; Glycocluster; Glycosaminoglycan.