title: A highly practical synthesis of the sialyl Lewis X pentasaccharide and an investigation of binding to E-, P-, and L-selectins.
abstract: A practical synthesis of the sialyl Lewis X (sLex) pentasaccharide, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta OEt (1), as a potential blocker for E-selectin has been described. The glycosylation of a trisaccharide acceptor, Fuc alpha (1-3)GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, did not yield the desired sLex pentasaccharide 1 at all. However, the glycosylation of a disaccharide acceptor, GlcNAc beta (1-3)Gal beta OEt, with a disaccharide donor, NeuAc alpha (2-3)Gal beta SMe, quantitatively yielded the tetrasaccharide NeuAc alpha (2-3)Gal beta (1-4)GlcNAc beta (1-3)Gal beta OEt. This tetrasaccharide is readily converted to the title compound in a high yield by fucosylation, followed by deprotection. The inhibitory activities of compound 1 toward the binding of the natural ligand (sLex) with the E-, P-, and L-selectins were stronger than those of the sLex tetrasaccharide.
authors.affiliation: Department of Medicinal Chemistry, Kanebo Ltd, New Drug Research Laboratories, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kiyoi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakai
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: M
authors.initials: M
authors.lastname: Kiso
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005643:Fucose / Q000378:metabolism; D006031:Glycosylation; D019041:L-Selectin / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
chemical_list: D000893:Anti-Inflammatory Agents; D019040:E-Selectin; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen; D019041:L-Selectin; D005643:Fucose