Synthesis of Neoglycolipid Analogues of the Oligosaccharide Portion of Ganglioside GM3

In order to elucidate the molecular specificity of the antimelanoma response induce by GM3 included in proteoliposome preparation, we designed syntheses of a series of neoglycolipids containing the trisaccharide portion of GM3 or its fragment. In the present paper, we synthesized two neoglicolipids containing as a lipid, a racemic glycerol unit substituted by two aliphatic octadecyl ether chains. The di‐ and trisaccharide derivatives were prepared as glycosides of the spacer by a sequence of isopropilidenation‐benzylation‐hydrolysis followed by sialylation. The condensation between the oligosaccharides and the lipid was performed by an amidation reaction.     

Lectin recognition of liposomes containing neoglycolipids. Influence of their lipidic anchor and spacer length

Eleven neoglycolipids were synthesized with a membrane anchor (cholesterol or Guerbet alcohols) attached, via a hydrophilic spacer, to a potential lectin-recognized sugar moiety (N-acetylglucosamine: GlcNAc). Neoglycolipids G24-0, G28-0 and G32-0, with a C₂₄, C₂₈ and C₃₂ Guerbet alcohol residue, had no spacer, while neoglycolipids G24-3, G28-3, G32-3 contained a triethoxy spacer. Cholesteryl neoglycolipids chol-1 to chol-4 and chol-7 contained one to four and seven ethoxy units. All the cholesteryl neoglycolipids were incorporated into liposomes, while, for the Guerbet derivatives, the presence (or not) of a spacer and the length of their alkyl chains played an important role for obtaining mixed liposomes. The abilities of liposomes to be recognized by wheat germ agglutinin (WGA) were measured as an increase of the absorbance at 450 nm. Significant WGA-induced aggregations were obtained with liposomes containing neoglycolipids chol-3, chol-4, chol-7, G28-3 and G32-3. As neoglycolipid G24-3 was not recognized, the accessibility of its GlcNAc moiety for WGA depended not only on the spacer length but on the nature of the anchor. The WGA-induced aggregations increased with increasing lectin concentrations until a maximum value, which depended on the nature of the neoglycolipid. The highest aggregation obtained with G28-3 and G32-3 occurred for a WGA–neoglycolipid mole ratio superior to the ratio observed with chol-3, chol-4 and chol-7. A preincubation of WGA with free GlcNAc did not inhibit the aggregation between WGA and mixed liposomes, demonstrating a greater affinity of WGA for the neoglycolipid GlcNAc than for free GlcNAc.