Introducing a C-interglycosidic bond in a biologically active pentasaccharide hardly affects its biological properties.
We describe here the synthesis and the biological activity of a 'C-pentasaccharide', a new analogue of the antithrombin III (AT III) binding region of heparin containing a methylene bridge in place of an interglycosidic oxygen atom. The affinity for AT III and the anti-factor Xa activity of this compound have been compared with that of the corresponding selected 'O-pentasaccharide'. Such a structural modification slightly decreased the affinity of this compound for AT III as well as its anti-factor Xa activity (880 +/- 40 anti-Xa units versus 1180 +/- 30 anti-Xa units for the C-pentasaccharide and the O-pentasaccharide, respectively). This compound therefore represents the first example of a new class of anti-factor Xa pentasaccharides containing a C-interglycosidic bond.
Petitou
M
M
Haemobiology Research Department, Sanofi Recherche, Toulouse, France.
Hérault
J P
JP
Lormeau
J C
JC
Helmboldt
A
A
Mallet
J M
JM
Sinaÿ
P
P
Herbert
J M
JM
D000990:Antithrombin III / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D065427:Factor Xa Inhibitors; D006027:Glycosides / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
D065427:Factor Xa Inhibitors; D006027:Glycosides; D009844:Oligosaccharides; D000990:Antithrombin III