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

Abstract

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.

• Authors: C T Yuen, K Bezouska, J O'Brien, M Stoll, R Lemoine, A Lubineau, M Kiso, A Hasegawa, N J Bockovich, K C Nicolaou
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 269 Issue 3 Pg. 1595-8 (Jan 21 1994) ISSN: 0021-9258 [Print] United States
• PMID: 7507478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• E-Selectin
• Lewis Blood Group Antigens
• Oligosaccharides
• Sulfates

Topics

• Animals
• Binding Sites
• CHO Cells
• Carbohydrate Conformation
• Carbohydrate Sequence
• Cell Adhesion (drug effects)
• Cell Adhesion Molecules (biosynthesis, metabolism)
• Cell Line
• Cricetinae
• E-Selectin
• Humans
• Lewis Blood Group Antigens (chemistry, metabolism)
• Magnetic Resonance Spectroscopy
• Molecular Sequence Data
• Oligosaccharides (chemical synthesis, chemistry, isolation & purification, pharmacology)
• Sulfates (analysis)
• Transfection