摘要 |
Tyrosine sulfate on PSGL-1, particularly at least one of residues 46, 48 and 51, functions in conjunction with sialylated and fucosylated glycans, most preferably Thr-57, to mediate high affinity binding to P-selectin. PSGL-1 O-glycans have been determined to consist of disialylated or neutral forms of the core-2 tetrasaccharide Gal beta 1->4GlcNAc beta 1->6(Gal beta 1->3)GalNAcOH. A minority of the O-glycans are alpha 1,3 fucosylated that occur as two major species containing the sialyl Lewis x antigen-one species is a disialylated monofucosylated glycan: - Fuc alpha 1 - &darr& - 3 - NeuAc alpha 2->3Gal beta 1->4GlcNAc beta 1 - &darr& - 6 - NeuAc alpha 2->3Gal beta 1->3GalNAc-R, - and the other is a monosialylated, trifucosylated glycan having a polylactosamine backbone: - Fuc alpha l - &darr& - 3 - NeuAc alpha 2->3Gal beta 1->4GlcNAc beta 1->3Gal beta 1-> - - Fuc alpha l Fuc alpha l - &darr& &darr& - 3 3 - 4GlcNAc beta 1->3Gal beta 1->4GlcNAc beta 1 - &darr& - 6 - Gal beta 1->3GalNAc-R - wherein R=H, OH, another sugar or an aglycone such as an amino acid, peptide, or polypeptide. The O-glycans defined herewith can be used to inhibit inflammation mediated by P-selectin. |