L-selectin interactions with novel mono- and multisulfated Lewisx sequences in comparison with the potent ligand 3′-sulfated Lewisa
L-selectin interactions with novel mono- and multisulfated Lewisx sequences in comparison with the potent ligand 3′-sulfated Lewisa
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DOI：
10.1074/jbc.274.26.18213
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发表时间：
1999-06-25
影响因子：
4.8
通讯作者：
Feizi, T
中科院分区：
文献类型：
--
作者：
Galustian, C;Lubineau, A;Feizi, T
The cell adhesion molecule L-selectin binds to 3'-sialyl-lewis (Le)(x) and -Le(a) and to 3'-sulfo-Le(x) and -Le(a) sequences, The binding to 3'-sialyl-Le(x) is strongly affected by the presence of 6-O-sulfate as found on oligosaccharides of the counter receptor, GlyCAM-1; 6-O-sulfate on the N-acetylglucosamine (6-sulfation) enhances, whereas 6-O-sulfate on the galactose (6'-sulfation) virtually abolishes binding. To extend knowledge on the specificity of L-selectin, we have investigated interactions with novel sulfo-oligosaccharides based on the Le(x) pentasaccharide sequence. We observe that, also with 3'-sulfo-Le(x), the B-sulfation enhances and 6'-sulfation suppresses L-selectin binding, The 6'-sulfation without 3'-sialyl or 3'-sulfate gives no binding signal with L-selectin, Where the 6-sulfo,3'-sialyl-Le(x) is on an extended di-N-acetyllactosamine backbone, additional 6-O-sulfates on the inner galactose and inner N-acetylglucosamine do not influence the binding. Although binding to the 6,3'-sulfo-Le(x) and 6-sulfo,3'-sialyl-Le(x) sequences is comparable, the former is a more effective inhibitor of L-selectin binding. This difference is most apparent when L-selectin is in paucivalent form (predominantly di- and tetramer) rather than multivalent, Indeed, as inhibitors of the paucivalent L-selectin, the 3'-sulfo-Le(x) series are more potent than the corresponding 3'-sialyl-Le(x) series. Thus, for synthetic strategies to design therapeutic oligosaccharide analogs as antagonists of L-selectin binding, those based on the simpler 3'-sulfo-Le(x) (and also the 3'-sulfo-Le(x)) would seem most appropriate.
