Design, synthesis and biological evaluation of aryl-substituted sialyl Lewis X mimetics prepared via cross-metathesis of C-fucopeptides.
Several aryl substituted C-fucopeptides have been developed as sialyl Lewis X mimetics. Although the compounds have a much simpler structure compared to SLe(x), up to 3-times higher binding affinity toward E-selectin and > 1000 times toward P-selectin was observed. Furthermore, a convenient strategy for generating a number of analogues from a SLe(x) mimetic template at a very late stage of the synthesis was introduced, using a ruthenium catalyzed cross olefin metathesis under benchtop conditions.
Huwe
C M
CM
Department of Chemistry and Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Woltering
T J
TJ
Jiricek
J
J
Weitz-Schmidt
G
G
Wong
C H
CH
D002240:Carbohydrate Sequence; D015195:Drug Design; D005643:Fucose / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry*; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
D009844:Oligosaccharides; D010455:Peptides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D005643:Fucose