Biol. Pharm. Bull. 30(9) 1697—1701 (2007)

genesis of hemolytic uremic syndrome (HUS) and severe systemic complications following enterohemorrhagic Escherichia coli (EHEC) infection in humans. Stxs have an AB5 structure, in which a single catalytic A subunit is associated with five identical B subunits. The B pentamer is responsible for the toxin binding to eukaryotic cell-surface glycolipid receptors such as galabiosyl (Gb2)-ceramide and globotriaosyl (Gb3)-ceramide. The susceptibility of target cells to Stxs is dependent on the presence of the functional glycolipid receptors. After binding, Stxs are internalized into the cells, and then the A subunit exerts RNA N-glycosidase activity, resulting in inhibition of protein synthesis by catalytic inactivation of 28S rRNA. Thus, the binding of Stxs to the receptor is the primary event causing Stx-mediated diseases. The binding of Stxs to the receptors is attributed to the interaction of the B pentamer with the saccharide moiety of the receptors. However, the Stxs do not strongly bind to the Gb3 monomer. It has been shown that Gb3 molecules are clustered and localized in lipid rafts on the cell membranes. The clustering of Gb3 molecules is important for strong binding to Stxs. In light of these findings, many synthetic compounds mimicking the natural receptors have been investigated for eliminating Stxs from the intestine and/or neutralizing Stxs in the circulation, as a therapeutic strategy for protecting patients from serious Stx-mediated diseases. All of these previously reported compounds possess repeated Gb3 mimic structures in a molecule with various backbones on expecting clustering effect of the saccharide moiety, although there was one exception of adamantyl-Gb3, 10) a Gb3 monovalent derivative, that was speculated to assemble into small aggregates for activity. In the present study, we synthesized novel Gb3and Gb2conjugated derivatives with a phosphatidyl residue, a sugar unit monomer in the chemical structure, which would be expected to form liposomes and clusters of the sugar unit to neutralize Stx-1 and Stx-2. These compounds showed strong neutralizing activity against not only Stx-1 but also Stx-2. In the present paper, we propose monovalent Gb3-/Gb2-derivatives conjugated with phosphatidyl residue as a new type of Stx-neutralizing agent.