title: Structure--activity relationships of sialyl Lewis x-containing oligosaccharides. 1. Effect of modifications of the fucose moiety.
abstract: Leukocyte adhesion to the vasculature is mediated by E-, P-, and L-selectins. The natural ligands for E- and P-selectins have not been fully characterized but have been shown to contain the tetrasaccharide sialyl Lewis x structure (SLe(x)). To determine the importance of the fucose moiety of SLe(x), various analogs of SLe(x) containing modifications thereof were prepared and tested as inhibitors of E-selectin-mediated cell adhesion. Cellular experiments indicate that replacement of the hydroxyl groups of fucose by hydrogen abrogated E-selectin binding. However, the arabinose analog of fucose (CH3 delta H) inhibited cell adhesion but was 5-fold less potent than native SLe(x). This data suggests that modifications of fucose on SLe(x) are generally deleterious toward E-selectin binding.
authors.affiliation: Department of Chemistry, Cytel Corporation, San Diego, California 92121.
authors.forename: J Y
authors.initials: JY
authors.lastname: Ramphal
authors.forename: Z L
authors.initials: ZL
authors.lastname: Zheng
authors.forename: C
authors.initials: C
authors.lastname: Perez
authors.forename: L E
authors.initials: LE
authors.lastname: Walker
authors.forename: S A
authors.initials: SA
authors.lastname: DeFrees
authors.forename: F C
authors.initials: FC
authors.lastname: Gaeta
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019040:E-Selectin; D005643:Fucose / Q000737:chemistry*; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D000080506:Sialyl Lewis X Antigen; D013329:Structure-Activity Relationship
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D005643:Fucose