SIALYL-LEWIS-X LIPOSOMES AS A MULTIVALENT LIGAND AND INHIBITOR OF E-SELECTIN MEDIATED CELLULAR ADHESION

A sialyl Lewis x-PEG-DSPE derivative (3) has been prepared using a com bined chemical enzymatic approach and incorporated into mPEG-DSPE cont aining liposomes (PEG, poly(ethylene glycol); mPEG, methoxypoly(ethyle ne glycol); DSPE, distearoylphosphatidylethanolamine). Several liposom al formulations of 3 were evaluated as inhibitors of E-selectin mediat ed cellular adhesion in an ELISA assay and were found to be similar to 750-fold more potent than the nonliposomal oligosaccharide (2) and gr eater than 5000-fold more potent than the natural glycotope structure (1). The dramatic increase in potency of the liposomal formulations su ggests that oligosaccharide multivalency enhances inhibition of E-sele ctin adhesion and is an effective approach to the design of more poten t selectin cell adhesion inhibitors.