Synthesis of the sialyl Lewis X epitope attached to glycolipids with different core structures and their selectin-binding characteristics in a dynamic test system.
Sialyl Lewis X (sLeX)/selectin-mediated leukocyte rolling along endothelial cells has recently gained wide interest. In this paper the influence of the spacer length of laterally clustered neoglycolipids 1a-d on cell rolling in a dynamic test system is investigated. The required di-O-hexadecyl glycerols with none, and with three, six, or nine ethylene glycol units as spacer groups (compounds 4a-d) could be readily obtained. The synthesis of 1-O-thexyldimethylsilyl-protected sLeX 24 was based on sialylation of 2,3,4-O-unprotected galactose derivative 11 with sialyl phosphite 8 as donor; this afforded the desired disaccharide 12, which was transformed into trichloroacetimidate 14 as disaccharide donor. Reaction of 3-O-unprotected glucosamine derivative 18 with fucosyl donor 20 afforded disaccharide 21, which was transformed into the 4-O-unprotected derivative 23. Reaction of 14 with 23 furnished the desired tetrasaccharide 24 in good yield. Transformation of 24 into the trichloroacetimidate 26 as donor, followed by the reaction with 4a-d as acceptor gave, after deprotection, the target molecules 1a-d. For comparison, 4d was also connected with a sialyl residue (-->31) and with an N-acetylglucosamine residue (-->34). Compounds 1c and 1d with a hexaethylene glycol and a nonaethylene glycol spacer, respectively, were much more efficient in mediating selectin-dependent cell rolling in the dynamic test system than compounds 1a and 1b, which had no spacer (1a), or only a triethylene glycol spacer (1b).
Gege
C
C
Fakultät für Chemie M726, Universität Konstanz, Germany.
Vogel
J
J
Bendas
G
G
Rothe
U
U
Schmidt
R R
RR
D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D002240:Carbohydrate Sequence; D002448:Cell Adhesion; D006224:Cricetinae; D000939:Epitopes / Q000737:chemistry; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D016256:Lewis X Antigen / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry* / Q000276:immunology; D019087:Selectins / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D013329:Structure-Activity Relationship
D000939:Epitopes; D006017:Glycolipids; D016256:Lewis X Antigen; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen