Synthesis of Conformationally Locked l-Iduronic Acid Derivatives: Direct Evidence for a Critical Role of the Skew-Boat 2S0 Conformer in the Activation of Antithrombin by Heparin

✍ Scribed by Sanjoy K. Das; Jean-Maurice Mallet; Jacques Esnault; Pierre-Alexandre Driguez; Philippe Duchaussoy; Philippe Sizun; Jean-Pascal Herault; Jean-Marc Herbert; Maurice Petitou; Pierre Sinaÿ

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 298 KB
• Volume: 7
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/1521-3765(20011119)7:22<4821::aid-chem4821>3.0.co;2-n

✦ Synopsis

We have used organic synthesis to understand the role of liduronic acid conformational flexibility in the activation of antithrombin by heparin. Among known synthetic analogues of the genuine pentasaccharidic sequence representing the antithrombin binding site of heparin, we have selected as a reference compound the methylated anti-factor Xa pentasaccharide 1. As in the genuine original fragment, the single l-iduronic acid moiety of this molecule exists in water solution as an equilibrium between three conformers 1 C 4 , 4 C 1 and 2 S 0 conformation of l-iduronic acid in the activation of antithrombin by heparin.