Identification of a hexasaccharide sequence able to inhibit thrombin and suitable for 'polymerisation'.
Three hexasaccharides, having from low to very high affinity for antithrombin, were synthesised from disaccharide building block precursors. One of them, methyl(sodium 2,3-di-O-methyl-4-O- sodium sulfonato-alpha-L-idopyranosyluronate)-(1-->4)-[(2,3,6-tri-O-sodiu m sulfonato-alpha-D-glucopyranosyl)-(1-->4)-(sodium 2,3-di-O-methyl-alpha-L-idopyranosyluronate)-(1-->4)]2-2,3,6-tri-O-sodiu m sulfonato-alpha-D-glucopyranoside, obtainable from a single disaccharide building block precursor, constitutes a good starting point for obtaining simple oligosaccharidic heparin mimetics able to inhibit the two coagulation factors thrombin and Factor Xa.
Duchaussoy
P
P
Sanofi Recherche, Haemobiology Research Department, Toulouse, France.
Jaurand
G
G
Driguez
P A
PA
Lederman
I
I
Gourvenec
F
F
Strassel
J M
JM
Sizun
P
P
Petitou
M
M
Herbert
J M
JM
D001665:Binding Sites; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009904:Optical Rotation; D011108:Polymers; D013917:Thrombin / Q000037:antagonists & inhibitors*
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D007202:Indicators and Reagents; D009844:Oligosaccharides; D011108:Polymers; D006493:Heparin; D013917:Thrombin