Spacer-separated sialyl LewisX cyclopeptide conjugates as potential E-selectin ligands

Completely protected sialyl LewisX azide was synthesized from a neolactosamine azide precursor carrying a 3-O-allyloxycarbonyl group as the temporary protecting group. After its Pd(0)-catalyzed deprotection and stereoselective alpha-fucosylation, the obtained LewisX azide was subjected to O-deacetylation in the galactose unit and subsequent regio- and stereoselective sialylation. Reduction of the anomeric azido group afforded the sialyl LewisX amine building block. Two molecules of this tetrasaccharide ligand were conjugated to a preformed cyclooctapeptide containing two equidistant L-asparagine units equipped with carboxy-terminated tetraethyleneglycol side chains to give, after deprotection, the target glycopeptide conjugate. Preliminary biological evaluation of the synthesized bivalent sialyl LewisX cyclopeptide conjugate showed only slightly enhanced inhibition of E-selectin binding in spite of the given flexibility of the two linked saccharide determinants. (c) 2006 Published by Elsevier Ltd.