E-selectin is the inducible adhesion
protein on the surface of endothelial cells which has a crucial role in the initial stages of recruitment of leucocytes to sites of
inflammation. In addition, it is almost certainly involved in
tumor cell adhesion and
metastasis. This report is concerned with identification of a new class of
oligosaccharide ligand--
sulfate-containing--for the human
E-selectin molecule from among
oligosaccharides on an ovarian
cystadenoma glycoprotein. This has been achieved by application of the neoglycolipid technology to
oligosaccharides released from the
glycoprotein by mild alkaline beta-elimination.
Oligosaccharides were conjugated to
lipid, resolved by thin-layer chromatography, and tested for binding by Chinese hamster ovary cells which had been transfected to express the full-length
E-selectin molecule. Several components with strong
E-selectin binding activity were revealed among acidic
oligosaccharides. The smallest among these was identified by liquid secondary ion mass spectrometric analysis of the neoglycolipid, in conjunction with methylation analysis of the purified
oligosaccharide preparation as an equimolar mixture of the Le(a)- and Le(x)/
SSEA-1-type fucotetrasaccharides sulfated at position 3 of outer
galactose: [formula: see text] To our knowledge this is the first report of a sulfofucooligosaccharide
ligand for
E-selectin. The binding activity is substantially greater than those of
lipid-linked Le(a) and Le(x)/
SSEA-1 sequences and is at least equal to that of the 3'-
sialyl-Le(x)/
SSEA-1 glycolipid analogue.