A CHEMICALLY SYNTHESIZED 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-GLUCOPYRA NNOSIDE, IS A POTENT INHIBITOR OF CELLULAR IMMUNE-RESPONSES

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 G(M3) ganglioside and a branched alkane in place of ceramide. It markedly inhibits the tetanus toxoid-induced human lymphoproliferative response in vitro (ID50<7 mu M) and is five-fold more active than d18:1-C18:0 G(M3) ganglioside, to which it is structurally related. This glycoconjugate is also a patent 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. (C) 1994 Academic Press, Inc.