Structure--activity relationships of sialyl Lewis x-containing oligosaccharides. 1. Effect of modifications of the fucose moiety.
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.
Ramphal
J Y
JY
Department of Chemistry, Cytel Corporation, San Diego, California 92121.
Zheng
Z L
ZL
Perez
C
C
Walker
L E
LE
DeFrees
S A
SA
Gaeta
F C
FC
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
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D005643:Fucose