Assessment through chemical synthesis of the size of the heparin sequence involved in thrombin inhibition

Deca- to eicosasaccharides having the generic structure methyl(sodium 2,3-di-O-methyl-4-O-sodium sulfonato-α-l-idopyranosyluronate)-(1→4)-[(2,3,6-tri-O-sodium sulfonato-α-d-glucopyranosyl)-(1→4)-(sodium 2,3-di-O-methyl-α-l-idopyranosyluronate)-(1→4)]n-2,3,6-tri-O-sodium sulfonato-α-d-glucopyranoside have been synthesized from a single disaccharide precursor. All of them bind to and activate antithrombin. When n≤6 only Factor Xa inhibition is observed, whereas when n>6 Factor Xa and thrombin are both inhibited in the presence of antithrombin. These results indicate that, in heparin, the sequence involved in antithrombin-catalyzed thrombin inhibition is a pentadeca- or a hexadecasaccharide.