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 combined chemical enzymatic
approach and incorporated into mPEG−DSPE containing liposomes (PEG,
poly(ethylene glycol); mPEG, methoxypoly(ethylene glycol); DSPE, distearoylphosphatidylethanolamine).
Several liposomal formulations of 3 were
evaluated
as inhibitors of E-selectin mediated cellular adhesion in an ELISA
assay and were found to be ∼750-fold more
potent than the nonliposomal oligosaccharide (2) and greater
than 5000-fold more potent than the natural glycotope
structure (1). The dramatic increase in potency of the
liposomal formulations suggests that oligosaccharide
multivalency enhances inhibition of E-selectin adhesion and is an
effective approach to the design of more potent
selectin cell adhesion inhibitors.