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-alpha-L-idopyranosyluronate)-(1 --> 4)-[(2,3,6-tri-O-sodium sulfonato-alpha-D-glucopyranosyl)-(1 --> 4)-(sodium 2,3-di-O-methyl-alpha-L-idopyranosyluronate) -( 1 --> 4)](n)-2,3,6-tri-O-sodium sulfonato-alpha-D-glucopyranoside have been synthesized from a single disaccharide precursor. All of them bind to and activate antithrombin. When n less than or equal to 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 pentadecaor a hexadecasaccharide. (C) 1999 Elsevier Science Ltd. All rights reserved.