Syntheses and evaluation of biantennary oligosaccharide ligands mimicking sialyl Lewis X.
Sialyl Lewis X (1) is known to be a ligand of the cell adhesion molecule E-selectin. We have synthesized several biantennary glycoside-terminated ligands mimicking sialyl Lewis X (1), and evaluated their binding activity to E-selectin using HL-60 cells expressing sialyl Lewis X epitope and human umbilical vein endothelial cells (HUVECs). These compounds were found to possess moderate binding activities to E-selectin. Among them, di-fucoside analog (8) which has no sialic acid carboxylate group was more active than 2, which had both the sialyl-galactose residue and the fucose residue (IC50, 8: 4.7 mM, 2: 11.7 mM). Furthermore, in the rat pleuritic model in vivo induced by carrageenin, 8 was found to reduce neutrophil infiltration at inflammatory lesions.
Sakagami
M
M
Drug Delivery System Institute, Ltd., Chiba, Japan.
Horie
K
K
Higashi
K
K
Yamada
H
H
Hamana
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002351:Carrageenan; D002448:Cell Adhesion; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D016256:Lewis X Antigen / Q000494:pharmacology*; D008024:Ligands; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010998:Pleurisy / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016256:Lewis X Antigen; D008024:Ligands; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D000080506:Sialyl Lewis X Antigen; D002351:Carrageenan