Bk. Brandley et al., STRUCTURE-FUNCTION STUDIES ON SELECTIN CARBOHYDRATE LIGANDS - MODIFICATIONS TO FUCOSE, SIALIC-ACID AND SULFATE AS A SIALIC-ACID REPLACEMENT, Glycobiology, 3(6), 1993, pp. 633-641
The selectins are a family of carbohydrate-binding proteins that have
been implicated in the initial interaction between leukocytes and the
vascular endothelium. The three members of this family will bind to th
e sialyl-Lewis(x) epitope [Sia alpha 2-3 Gal beta 1-4 (Fuc alpha 1-3)
GlcNAc] and related oligosaccharides. In this report, we examine the m
olecular details of that recognition using synthesized carbohydrates w
ith specific modifications on the sialyl-Lewis(x) epitope. E- and L-Se
lectin require hydroxyl groups at the 2, 3 and 4 positions of the fuco
se residue. P-Selectin, however, requires only the 3-position hydroxyl
group, while tolerating removal of the oxygen at positions 2 or 4 of
fucose residue. Modifications of the glycerol side chain or the N-acet
yl group of the sialic acid have little effect an the binding of any o
f the selectins. All three selectins bind efficiently to an oligosacch
aride with a sulphate replacement for the sialic acid [sulpho-Lewis(x)
, or SO4-3Gal beta 1-4 (Fuc alpha 1-3) Glc-ceramide]. For E-Selectin,
binding to sulpho-Lewis(x) appears to be equivalent to binding to sial
yl-Lewis(x), while for L- and P-Selectin binding to the sulphated stru
cture shows characteristics distinct from sialyl-Lewis(x) recognition.
Taken together, these data indicate that, while all three selectins c
an recognize sialyl-Lewis(x), E-, L- and P-Selectin each display disti
nct carbohydrate ligand preferences.