Synthesis of new conformationally constrained pentasaccharides as molecular probes to investigate the biological activity of heparin.
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.
Sisu
Eugen
E
Ecole Normale Supérieure, Département de Chimie Associé au CNRS, 24, rue Lhomond, 75231 Paris cedex 5, France.
Tripathy
Sasmita
S
Mallet
Jean-M
JM
Driguez
Pierre-A
PA
Hérault
Jean-P
JP
Sizun
Philippe
P
Herbert
Jean-M
JM
Petitou
Maurice
M
Sinay
Pierre
P
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
D000991:Antithrombins; D006023:Glycoproteins; D015335:Molecular Probes; D009844:Oligosaccharides; D013431:Sulfates; D007067:Iduronic Acid; D000990:Antithrombin III; D006493:Heparin