Author/Authors :
Anne Marinier، نويسنده , , Alain Martel، نويسنده , , Carol Bachand، نويسنده , , Serge Plamondon، نويسنده , , Brigitte Turmel، نويسنده , , Jean-Paul Daris، نويسنده , , Jacques Banville، نويسنده , , Philippe Lapointe، نويسنده , , Carl Ouellet، نويسنده , , Pierre Dextraze، نويسنده , , Marcel Menard، نويسنده , , John J.K Wright، نويسنده , , Julie Alford، نويسنده , , Debbie Lee، نويسنده , , James Paul Stanley، نويسنده , , Xina Nair، نويسنده , , Gordon Todderud، نويسنده , , Kenneth M. Tramposch، نويسنده ,
Abstract :
A series of potent inhibitors of P-selectin as potential anti-inflammatory agents is reported. These compounds are derivatives of galactocerebrosides bearing a malonate side chain in positions 2 and 3 of the galactose moiety. Based on the binding mode of sialyl Lewis X, the two acidic groups of the malonate are designed to form ionic interactions with two important lysines in the active site of P-selectin, Lys113 and Lys111. On the other hand, the 4- and 6-hydroxy groups on the galactose ring are arranged to chelate the calcium ion in the P-selectin active site. The synthesis and the biological activity of this series of compounds are described. Lead compounds having a greater potency than sialyl Lewis X are identified.
