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 residue has been deoxygenated at position three. 1H NMR studies demonstrated that, as anticipated, such a modification induces a shift of the conformational equilibrium toward 1C4 (contribution to the conformational equilibrium rises from 37% to 65%) and a substantial decrease of the affinity for antithrombin III (Kd 0.154 microM versus 0.050 microM).
Lei
P S
PS
Ecole Normale Supérieure, Département de Chimie, URA CNRS 1686, Paris, France.
Duchaussoy
P
P
Sizun
P
P
Mallet
J M
JM
Petitou
M
M
Sinaÿ
P
P
D000990:Antithrombin III / Q000378:metabolism*; D001665:Binding Sites; D002240:Carbohydrate Sequence; D006493:Heparin / Q000138:chemical synthesis* / Q000737:chemistry; D007067:Iduronic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D015335:Molecular Probes / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry
D015335:Molecular Probes; D009844:Oligosaccharides; D007067:Iduronic Acid; C049714:IC 831423; D000990:Antithrombin III; D006493:Heparin