LIGAND INTERACTIONS WITH E-SELECTIN - IDENTIFICATION OF A NEW BINDING-SITE FOR RECOGNITION OF N-ACYL AROMATIC GLUCOSAMINE SUBSTITUENTS OF SIALYL-LEWIS-X

Several N-acylglucosamine derivatives of sialyl Lewis X (1-3) were pre pared using a combined chemical enzymatic approach and evaluated as an inhibitor of E-selectin-mediated cellular adhesion. Compounds with ar omatic functionality, 1 and 2, were found to be 3-10 times more potent than the N-acetyl derivative (14) in, an ELISA E-selectin cell adhesi on assay. Conformational analysis with NMR indicated that the sialyl L ewis x domain of 1 retained the conformation of the N-acetyl derivativ e (14) despite the presence of the N-naphthamido group. The dramatic o rder of magnitude increase in potency of these monovalent structures c an be utilized to design more potent selectin-based cell adhesion inhi bitors.