Synthesis of novel 6-amido-6-deoxy-l-galactose derivatives as sialyl Lewis X mimetics.
The synthesis and biological potency of several sialyl Lewis X (SLe(x)) mimetics is described. These mimics incorporate all of the critical functional groups present in SLe(x) necessary for binding to E-selectin. L-Galactose is used to mimic the naturally occurring L-fucose residue in SLe(x) due to the identical arrangement of the 2-, 3-, and 4-hydroxyl groups. Several synthetically and enzymatically prepared amino acids were used to mimic the D-galactose residue. Because of the variability incorporated in the synthesis of these amino acids the spatial requirements necessary for efficient binding were investigated. A carboxylate bearing side chain was introduced as a sialic acid mimic and the chain length was varied to maximize biological activity. By investigating the optimal arrangement of these two factors mimics were produced which were up twofold more active than SLe(x).
Cappi
M W
MW
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Moree
W J
WJ
Qiao
L
L
Marron
T G
TG
Weitz-Schmidt
G
G
Wong
C H
CH
D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D005643:Fucose / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009844:Oligosaccharides / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism
D000588:Amines; D000596:Amino Acids; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D005643:Fucose