Studies on selectin blocker. 1. Structure-activity relationships of sialyl Lewis X analogs

As a part of our studies of selectin blockers, we prepared 1-deoxy-3'-O- sulfo Le(x) analogs (1-3), 1-deoxy-3'-O-phosphono Le(x) analogs (4), and 1- deoxy sLe(x) analogs (5-7), and examined their inhibitory activities against natural ligand (sLe(x)) binding to E-selectin, P-selectin, and L-selectin. The 1-deoxy sLe(x) 5 was up to 20 times more potent an inhibitor than the sLe(x) tetrasaccharide toward P- and L-selectin binding. This indicates that the modification of the 1 or 2 position of sLe(x) is useful in the design of a more potent selectin blocker.