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

作者：Chun-Ting Yuen, Karel Bezouška, J. O'Brien, Mark S. Stoll, Rémy C. Lemoine, André Lubineau, Makoto Kiso, Akira Hasegawa, Nicholas J. Bockovich, Kyriacos Costa Nicolaou · 发表于：Journal of Biological Chemistry · 年份：1994 · DOI：10.1016/s0021-9258(17)42065-5 · 被引用次数：148 · 研究领域：Cell Adhesion Molecules Research、Glycosylation and Glycoproteins Research、Monoclonal and Polyclonal Antibodies Research

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 importan...