Synthesis of a 3-deoxy-l-iduronic acid containing heparin pentasaccharide to probe the conformation of the antithrombin III binding sequence Original Research Article

We report in this work the total synthesis of a close analogue of the pentasaccharide active site of heparin, in which the l-iduronic acid residue has been deoxygenated at position three. 1H NMR studies demonstrated that, as anticipated, such a modification induces a shift of the conformational equilibrium toward 1C4 (contribution to the conformational equilibrium rises from 37% to 65%) and a substantial decrease of the affinity for antithrombin III (Kd 0.154 μM versus 0.050 μM).