title: A chemically synthesized sialic acid-containing glycoconjugate, 2-(tetradecylhexadecyl)-O-(5-acetamido-3,5-dideoxy-D-glycero-alpha-D-ga lacto-2-nonulopyranosylonic acid)-(2-->3)-O-beta-D-galactopyrannosyl-(1-->4)-beta-D- glucopyrannoside, is a potent inhibitor of cellular immune responses.
abstract: Structural variations among gangliosides significantly influence their immunosuppressive activity. By total chemical synthesis, a sialic acid-containing glycoconjugate, 2-(tetradecylhexadecyl)-O-(5-acetamido-3,5-dideoxy-D-glycero-alpha -D-galacto-2-nonulopyranosylonic acid)-(2-->3)-O-beta-D-galactopyrannosyl-(1-->4)-beta-D- glucopyrannoside was synthesized. This glycoconjugate has the same carbohydrate structure as does GM3 ganglioside and a branched alkane in place of ceramide. It markedly inhibits the tetanus toxoid-induced human lymphoproliferative response in vitro (ID90 < 7 microM) and is five-fold more active than d18:1-C18:0 GM3 ganglioside, to which it is structurally related. This glycoconjugate is also a potent inhibitor of the murine alloimmune response in vivo: 10 nmol of the molecule injected subcutaneously together with an allogeneic cell challenge markedly inhibits the cellular immune response in the draining popliteal lymph node. In fact, the effect is quantitatively similar to that of systemically administered cyclosporin A, a well-studied immunosuppressive agent.
authors.affiliation: Center for Cancer and Transplantation Biology, Children's Research Institute, Washington, DC 20010.
authors.forename: S
authors.initials: S
authors.lastname: Ladisch
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Kiso
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology; D005679:G(M3) Ganglioside / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid; D012794:Sialic Acids; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D013745:Tetanus Toxoid / Q000494:pharmacology; D014312:Trisaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D005679:G(M3) Ganglioside; C089430:GSC 53; D007166:Immunosuppressive Agents; D012794:Sialic Acids; D013745:Tetanus Toxoid; D014312:Trisaccharides; D016572:Cyclosporine; D019158:N-Acetylneuraminic Acid