title: Synthetic studies on selectin ligands/inhibitors. Synthesis and biological evaluation of sulfated and phosphorylated beta-D-galacto- and lactopyranosides containing fatty-alkyl residues of different carbon chain lengths.
abstract: To investigate the biological selectin-ligand interactions, fourteen sulfated and eight phosphorylated beta-D-galacto- and lactopyranosides containing branched fatty-alkyl residues in place of the ceramide have been synthesized. Regioselective sulfation of the parent glycolipids through the dibutylstannylene acetal with a certain amount of sulfur trioxide-trimethylamine complex produced the target sulfated glycolipids, while stepwise phosphorylation by treatment of the properly protected diol with dibenzyloxy(diisopropylamino)phosphine gave the phosphorylated glycolipids. The synthetic glycolipids showed an interesting mode of inhibition of the binding of HL-60 cells to immobilized P-, L- and E-selectins during in vitro experiments. In addition, using computer modeling techniques, we examined the molecular basis for the ligand-selectin complex formation. These glycolipids may be useful as therapeutic agents against selectin-dependent inflammation.
authors.affiliation: Drug Discovery Research Department, Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ikami
authors.forename: N
authors.initials: N
authors.lastname: Tsuruta
authors.forename: H
authors.initials: H
authors.lastname: Inagaki
authors.forename: T
authors.initials: T
authors.lastname: Kakigami
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: N
authors.initials: N
authors.lastname: Tomiya
authors.forename: T
authors.initials: T
authors.lastname: Jomori
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: D
authors.initials: D
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Ishida
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Kiso
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015195:Drug Design; D005697:Galactosides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005697:Galactosides; D006027:Glycosides; D008024:Ligands; C008245:lactosides