Potentiation of the tolerogenicity of benzylpenicilloylated eicosa-L-lysine by conjugation with 4-(hydroxymethyl)benzyl 3 beta-cholestanyl succinate.

It was previously found that amino acid polymers such as oligolysines bearing haptenic groups in high densities efficiently suppress anti-hapten IgE antibody formation. Such conjugates are strong elicitors of anaphylaxis and therefore may not be used for desensitization of drug allergic patients. Here we report on the synthesis and immunological evaluation of benzylpenicilloylated (BPO) eicosa-L-lysines containing none, one, or two lipophilic p-(hydroxymethyl)benzyl cholestan-3 beta-yl succinate (OSuco) groups. The lipophilic derivatives suppress primary as well as ongoing anti-BPO IgE antibody formation in mice much more efficiently than their hydrophilic counterpart. The lipophilic but not the hydrophilic derivatives form stable micelles in water and suppress the antibody formation according to different cellular mechanisms. The relationship between structure, hydrophobicity, and mode of action is discussed.