Studies on Selectin Blocker. 1. Structure−Activity Relationships of Sialyl Lewis X Analogs

Abstract

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.