title: Studies on selectin blockers. 2. Novel selectin blocker as potential therapeutics for inflammatory disorders.
abstract: As a part of our studies of selectin blockers, we prepared 1-(2-tetradecylhexadecyl)-3'-O-sulfo Le(X) 1 and 1-(2-tetradecylhexadecyl) sLe(X) 2 and examined their inhibitory activities against natural ligand (sLe(X)) binding to E-, P-, and L-selectins. Compounds 1 and 2 were 2 times more potent than the sLe(X) tetrasaccharide toward E-selectin binding and up to 4 times more potent than sLe(X) toward P- and L-selectin binding. Interestingly, compound 1 provided dose-dependent protective effects against an immunoglobulin E-mediated skin reaction in mouse ears. This protective effect was associated with diminished tissue accumulation of neutrophils in the ear (as assessed by myeloperoxidase). These findings indicate that the modification of sLe(X) or 3'-O-sulfo Le(X) with a "branched anchor", a 2-tetradecylhexadecyl group, is useful in the design of a more potent selectin blocker, which has broad inhibitory activities toward all selectins.
authors.affiliation: New Drug Research Laboratory, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: N
authors.initials: N
authors.lastname: Matsuda
authors.forename: H
authors.initials: H
authors.lastname: Ohmoto
authors.forename: K
authors.initials: K
authors.lastname: Yoshino
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
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: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use*; D002240:Carbohydrate Sequence; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D019087:Selectins / Q000187:drug effects*; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C099632:2-tetradecylhexadecyl O-(3-O-sulfogalactopyranosyl)-1-4-O-(fucopyranosyl-1-3)glucopyranoside; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009844:Oligosaccharides; D019087:Selectins; D013463:Sulfuric Acid Esters