Sialyl Lewis(x) analogs based on a quinic acid scaffold as the fucose mimic.
(-)-Quinic acid was used as a starting material for the preparation of sialyl Lewis(x) mimetics in order to target E-selectin. Spatial orientation of the hydroxyl groups of quinic acid could mimic the l-fucose ones. Introduction of a side chain ending with a carboxylic acid was effected to replace the sialic acid interaction at the carbohydrate recognition domain. A first series of derivatives, incorporating amino acids linked to quinic acid, were tested for their affinity and found to interact with E-selectin with IC(50) within the millimolar range.
Girard
Christian
C
Laboratoire de Pharmacologie Chimique and Génétique (UMR 8151 CNRS/U 640 INSERM), Ecole Nationale Supérieure de Chimie de Paris, 11 rue P. and M. Curie, 75005 Paris, France. christian-girard@enscp.fr
Dourlat
Jennifer
J
Savarin
Aline
A
Surcin
Christine
C
Leue
Stefanie
S
Escriou
Virginie
V
Largeau
Céline
C
Herscovici
Jean
J
Scherman
Daniel
D
D002448:Cell Adhesion / Q000187:drug effects; D019040:E-Selectin / Q000187:drug effects* / Q000378:metabolism; D005643:Fucose / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D019007:P-Selectin / Q000187:drug effects; D011801:Quinic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D000080506:Sialyl Lewis X Antigen
D019040:E-Selectin; D008024:Ligands; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; D011801:Quinic Acid; D005643:Fucose