Synthesis of new conformationally constrained pentasaccharides as molecular probes to investigate the biological activity of heparin

Abstract

We have synthesized three new antithrombin activating pentasaccharides displaying various sulfation patterns on the reducing end unit (H). We found that when L-iduronic acid stands in the 2S(0) conformation, the sulfate groups at positions 3 and 6 of the reducing end unit are practically devoid of influence on the activation of antithrombin. This suggests that the positive role of these sulfates is more related to their ability to shift the conformational equilibrium of L-iduronic acid towards 3S(0) than to directly interact with the protein.