title: 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.
authors.affiliation: Ecole Normale Supérieure, Département de Chimie Associé au CNRS, 24, rue Lhomond, 75231 Paris cedex 5, France.
authors.forename: Eugen
authors.initials: E
authors.lastname: Sisu
authors.forename: Sasmita
authors.initials: S
authors.lastname: Tripathy
authors.forename: Jean-M
authors.initials: JM
authors.lastname: Mallet
authors.forename: Pierre-A
authors.initials: PA
authors.lastname: Driguez
authors.forename: Jean-P
authors.initials: JP
authors.lastname: Hérault
authors.forename: Philippe
authors.initials: P
authors.lastname: Sizun
authors.forename: Jean-M
authors.initials: JM
authors.lastname: Herbert
authors.forename: Maurice
authors.initials: M
authors.lastname: Petitou
authors.forename: Pierre
authors.initials: P
authors.lastname: Sinay
mesh_terms: D000990:Antithrombin III / Q000737:chemistry / Q000378:metabolism; D000991:Antithrombins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D007067:Iduronic Acid / Q000737:chemistry / Q000378:metabolism; D015335:Molecular Probes; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism
chemical_list: D000991:Antithrombins; D006023:Glycoproteins; D015335:Molecular Probes; D009844:Oligosaccharides; D013431:Sulfates; D007067:Iduronic Acid; D000990:Antithrombin III; D006493:Heparin