SYNTHESIS OF A 3-DEOXY-L-IDURONIC ACID-CONTAINING HEPARIN PENTASACCHARIDE TO PROBE THE CONFORMATION OF THE ANTITHROMBIN-III BINDING SEQUENCE

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 r esidue has been deoxygenated at position three. H-1 NMR studies demons trated that, as anticipated, such a modification induces a shift of th e conformational equilibrium toward C-1(4) (contribution to the confor mational equilibrium rises from 37% to 65%) and a substantial decrease of the affinity for antithrombin III (K-d 0.154 mu M versus 0.050 mu M). (C) 1998 Elsevier Science Ltd. All rights reserved.