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.
Highlights
Jacqui O'Brient, MarkStollS, Remy Lemoinell, inhibitors that may serve as drugs for the treatment of disor
One of the binding of the endothelial adhesion molecule, E-selec- active oligosaccharidefractions was identified as an equimolar tin, was identified as anequimolar mixtureof tetrasac- mixture of the Lea- and Lex-type tetrasaccharides sulfated at charides of blood group Le" and Le' type sulfated at position 3 of the outer galactose, as shown below
E-selectin Binding Assays-E-selectin binding to lipid-linked oligo- volumes 50 pl; 210 pl of the 3H-labeled SC2 cellsuspension were saccharides chromatographed on silica gel plates was detected by fluo- added to each well and mixed gently before sealing the plates with rography using [3Hlthymidine-labeledChinese hamster ovary (CHO)3 plastic tape
Summary
For ease of comparison of the sialylated Le" and L e x sequences with the sulfated analogues, the terms tri, tetra, and penta are used for the fuco-oligosaccharidemoieties, trisaccharides, tetrasaccharides, and pentasaccharides that arecommon to the two types of acidic oligosaccharides. Sulfated Le" tri (Sua3) Sulfated Le" tetra (Su-4) Sulfated Le" penta (Su85) Sialyl Le" tri Sialyl Le" penta (S"5)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have