[Oligosaccharide sulfate inhibitors of selectin-sugar interactions in inflammatory processes].
Leucocyte migration into lymphatic tissues or inflammatory sites depends upon the expression of adhesion molecules. Among these molecules, the selectins expressed on endothelial cells (E- and P-selectins) and leucocytes (L-selectin) recognize carbohydrate ligands such as sialyl Lewis A or sialyl Lewis X oligosaccharides due to the same positioning of NeuAc, Gal and Fuc residues in both isomeric structures. We have shown that the sialic acid residue could be replaced by a sulfate group such as in the sulfated Lewis A pentasaccharide, one of the most potent monovalent ligand for human E-selectin, which was shown to be very active in the prevention of ischemia reperfusion lung injury. In the same way, we have prepared through chemoenzymatic syntheses, two disulfated Lewis X pentasaccharides, the sulfated analogs of carbohydrate ligands found on GLYCAM 1, the natural receptor of L-selectin. Finally, based on the double recognition of L-selectin with Lewis type and glycosaminoglycan structures, we tentatively introduced a possible link between the selectin- and the integrin-mediated lymphocyte adhesion systems.
Auge
C
C
Laboratoire de Chimie Organique Multifonctionnelle, Institut de Chimie Moléculaire d'Orsay, Université Paris-Sud, Orsay.
Dagron
F
F
Lemoine
R
R
Le Narvor
C
C
Lubineau
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology; D019087:Selectins / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009844:Oligosaccharides; D019087:Selectins
Oligosaccharides sulfatés inhibiteurs des interactions sélectines-sucres intervenant dans les processus inflammatoires.