Lectin-mediated aggregation of liposomes containing glycolipids with variable hydrophilic spacer arms

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Abstract
Synthetic glycolipids containing a cholesterol anchor group attached via a spacer group to a sugar moiety can be incorporated into small unilamellar liposomes, rendering them susceptible to agglutination by the appropriate multivalent lectin. The role of spacer arm length in rendering these liposomes susceptible to agglutination is reported. In order to eliminate the ambiguities inherent in using hydrophobic or charged spacer groups, a hydrophilic, ethylene glycol based amino acid (8-amino-3,6-dioxaoctanoic acid) was synthesized for these studies. The Ricinus communis agglutinin (ricin) mediated agglutination of these .beta.-galactoside-containing glycolipids was studied. A spacer arm length of 4 atoms will not support agglutination under any conditions. A 7-atom spacer will support agglutination, but only at high phospholipid concentrations (0.24 .mu.mol/ml) with a pseudo-1st-order rate of agglutination of 0.0079 min-1. With 13 and 22 atom spacer groups, the pseudo-1st-order rate constants were 0.4 min-1 and 1.3 min-1, respectively, at a phospholipid concentration of 0.06 .mu.mol/ml. Under conditions where the liposomes containing the glycolipid with the 13-atom hydrophilic spacer arm were completely agglutinated by ricin, 9.3% of the total available sugar moieties of the liposome were bound to ricin. This means that, on the average, 38 interliposomal bonds were formed in an aggregate.