Sulfated blood group Lewis(a). A superior oligosaccharide ligand for human E-selectin

• Published in: The Journal of biological chemistry Vol. 269; no. 3; pp. 1595 - 1598
• Main Authors: Yuen, C T, Bezouska, K, O'Brien, J, Stoll, M, Lemoine, R, Lubineau, A, Kiso, M, Hasegawa, A, Bockovich, N J, Nicolaou, K C
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 21-01-1994
• Subjects: Animals; Binding Sites; Carbohydrate Conformation; Carbohydrate Sequence; Cell Adhesion - drug effects; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - metabolism; Cell Line; CHO Cells; Cricetinae; E-Selectin; Humans; Lewis Blood Group Antigens - chemistry; Lewis Blood Group Antigens - metabolism; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Oligosaccharides - chemical synthesis; Oligosaccharides - chemistry; Oligosaccharides - isolation & purification; Oligosaccharides - pharmacology; Sulfates - analysis; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)42065-5

In earlier studies of oligosaccharide probes (neoglycolipids) generated from an ovarian cystadenoma glycoprotein, one of the
components that strongly supported binding of the endothelial adhesion molecule, E-selectin, was identified as an equimolar
mixture of tetrasaccharides of blood group Le(a) and Le(x) type sulfated at position 3 of the outer galactose (C.-T. Yuen,
A. M. Lawson, W. Chai, M. Larkin, M. S. Stoll, A. C. Stuart, F. X. Sullivan, T. J. Ahern, and T. Feizi (1992) Biochemistry
31, 9126-9131). In the present studies, the individual sulfated Le(a) and sulfated Le(x) oligosaccharides synthesized chemically
have been investigated, first, for their ability to support E-selectin binding when converted into neoglycolipids, and second,
for their ability to inhibit E-selectin binding to immobilized lipid-linked sialyl-Le(a), sialyl-Le(x), or sulfated Le(a)
pentasaccharides; their activities have been compared with those of the sialyl-Le(a) and sialyl-Le(x) analogues. From these
studies, the sulfated Le(a) tetra- and pentasaccharides emerge as the most potent E-selectin ligands so far. In particular,
the inhibitory activity of the sulfated Le(a) pentasaccharide is substantially greater than that of the sialyl-Le(x) trisaccharide,
which is currently the most widely used inhibitor of E-selectin binding: 45-, 35-, or 15-fold greater depending on whether
adhesion is to sialyl-Le(a), sulfated Le(a), or sialyl-Le(x) pentasaccharides, respectively. These findings have an important
bearing on design of new generations of inhibitors of E-selectin binding as antiinflammatory compounds.