Anticoagulant properties of dextranmethylcarboxylate benzylamide sulfate (DMCBSu); a new generation of bioactive functionalized dextran

Dextranmethylcarboxylate benzylamide sulfate (DMCBSu), a functionalized dex tran, exhibits anticoagulant properties. Its synthesis involves three steps : a carboxymethylation with monochloroacetic acid in alkaline water-isoprop anol, a benzylamidification of some of the methylcarboxylate groups with be nzylamine in the presence of a water soluble carbodiimide and a partial sul fation of the remaining hydroxyl groups with SO3-pyridine in dimethylformam ide. This procedure yields reproducibly DMCBSu with degrees of substitution in methylcarboxylate (MC), benzylamide (B) and sulfate (Su) groups, respec tively, up to 1.61, 0.35 and 1.5, each obtained in one step. For a degree o f substitution of methylcarboxylate ca. 1, the presence of sulfate groups i s absolutely necessary to confer anticoagulant activities to the samples. I n addition, the anticoagulant ability is higher for derivatives bearing ben zylamide groups. The anticoagulant ability of DMCBSu increases with the deg ree of sulfation, reaching 20% of heparin activity for a degree of substitu tion of Su groups about 1.3. (C) 2001 Elsevier Science Ltd. All rights rese rved.