Monovalent Gb₃-/Gb₂-Derivatives Conjugated with a Phosphatidyl Residue: A Novel Class of Shiga Toxin-Neutralizing Agent

抄録

Shiga toxin (Stx) exerts toxic activity by binding to glycosphingolipids, mainly globotriaosyl (Gb₃) ceramide, on the surface of target cells. The inhibition of toxin-receptor binding is a promising therapeutic approach to prevent Stx-mediated diseases. In this study, we synthesized monovalent Stx-ligands of phosphatidylethanolamine dipalmitoyl-Gb₃ (Gb₃-PEDP) and galabiosyl (Gb₂)-PEDP and we examined their neutralizing activity against Stx-1 and Stx-2 in vitro. Both Gb₃-PEDP and Gb₂-PEDP strongly neutralized the cytotoxicity of Stx-1 and Stx-2. It is likely that the mechanism of neutralization involved formation of liposomes and consequently clustering of sugar units. We propose monovalent Gb₃-/Gb₂-derivatives conjugated with phosphatidyl residue as a novel class of Stx-neutralizing agent.