Synthesis and Properties of Heparin Derivatives

Abstract

The most pronounced actions of heparin are its anticoagulant effect and its promotion of the clearance of chylomicrons and various lipoproteins from the bloodstream. In both activities, heparin is far more efficient than any available synthetic materials. Two restricting factors in its use are that it has to be administered intravenously and that its effect is comparatively short-lived (5, 10–12). The aims of current studies on chemical modification of heparin therefore include the synthesis of products that would be cleared more slowly from the circulation and the preparation of materials that might be absorbed from the intestine. Another aim is to make it possible to use heparin that is modified at specific sites for investigating the mechanism of its action. It would be of interest to obtain derivatives with only one of the biologic activities - lipid clearance or anticoagulation. The other purpose in studying heparin modification is to elucidate the mechanism of its actions. This is complicated by the lack of definition of the processes involved in the release and activation of lipoprotein lipase and in the individual steps of the blood coagulation sequence. However, some aspects of the mechanisms are amenable to study with heparin derivatives.