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L-selectin Interactions with Novel Mono- and Multisulfated Lewisx Sequences in Comparison with the Potent Ligand 3'-Sulfated Lewis(a).

Galustan, Christine and Lubineau, André and le Narvor, Christine and Kiso, Makoto and Brown, Gavin M. and Feizi, Ten (1999) L-selectin Interactions with Novel Mono- and Multisulfated Lewisx Sequences in Comparison with the Potent Ligand 3'-Sulfated Lewis(a). Journal of Biological Chemistry, 274 (26). pp. 18213-18217.

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Abstract

The cell adhesion molecule L-selectin binds to 3'-sialyl-Lewis (Le)x and -Lea and to 3'-sulfo-Lex and -Lea sequences. The binding to 3'-sialyl-Lex 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 Lex pentasaccharide sequence. We observe that, also with 3'-sulfo-Lex, the 6-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-Lex 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-Lex and 6-sulfo,3'-sialyl-Lex 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-Lex series are more potent than the corresponding 3'-sialyl-Lex series. Thus, for synthetic strategies to design therapeutic oligosaccharide analogs as antagonists of L-selectin binding, those based on the simpler 3'-sulfo-Lex (and also the 3'-sulfo-Lea) would seem most appropriate.

Item Type: Article
Journal or Publication Title: Journal of Biological Chemistry
Subjects: Q Science > QH Natural history > QH301 Biology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
VC's Office
ID Code: 9060
Deposited By: Dr Gavin M Brown
Deposited On: 23 May 2008 13:57
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 18:31
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/9060

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