Location on Heparin of the Oligosaccharide Section Essential for Anticoagulant Activity

Studies were conducted to define the location of the unique oligosaccharide sequence in heparin that is required for its anticoagulant activity. A heparin fraction with an average molecular weight of 20,000 was linked at its reducing terminus to a Sepharose derivative via an azo bridge. The matrix-linked heparin was subjected to limited degradation with nitrous acid and, after the cleaved segments were removed, the section contiguous with the original reducing terminus was released from the gel by treatment with sodium dithionite. The results of analyses of the products after separation into different molecular weight pools demonstrate that the groups responsible for accelerating the neutralization of thrombin and Factor Xa by antithrombin are located at or near the nonreducing terminus of the heparin chain.