Aliphatic Polyethers with Sulfate, Carboxylate, and Hydroxyl Side Groups-Do They Show Anticoagulant Properties?

Abstract

There is increasing interest in the synthesis of low molecular weight heparin and heparan sulfate mimetic polymers because of their various potential biomedical applications. The functional activity of heparin and heparan sulfate is believed to arise from the presence of a number of functional groups, such as hydroxyl, carboxylate and sulfate groups. The design and synthesis of novel heparin-mimetic polymers with a particular functionality poses a formidable challenge and requires carefully control of the selective conversion of functional groups on the polymer chain. Here, this study describes a simple and efficient synthetic protocol for the preparation of heparin-mimetic linear polyglycidol copolymers based on the selective conversion of primary hydroxyl groups to carboxylic acids under ruthenium-catalyzed selective dehydrogenation in basic aqueous solution. To achieve the anticoagulant activity of these polymers, primary hydroxyl groups are selectively converted to sulfate groups. The anticoagulant activity of the heparin mimics is studied by rotational thromboelastometry using EXTEM and INTEM assays. The environmentally benign process described herein provides an attractive route for the synthesis of heparin-mimetic polymers with tailored functions such as anticoagulant activity.