Monovalent Gb3-/Gb2-derivatives conjugated with a phosphatidyl residue:: A novel class of Shiga toxin-neutralizing agent
Monovalent Gb3-/Gb2-derivatives conjugated with a phosphatidyl residue:: A novel class of Shiga toxin-neutralizing agent
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DOI：
10.1248/bpb.30.1697
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发表时间：
2007-09-01
影响因子：
2
通讯作者：
Mori, Hiroshi
中科院分区：
文献类型：
--
作者：
Neri, Paola;Tokoro, Shunji;Mori, Hiroshi
志贺毒素 (Stx) 通过与靶细胞表面的鞘糖脂（主要是三糖基 (Gb(3)) 神经酰胺）结合而发挥毒性活性。抑制毒素受体结合是预防 Stx 介导的疾病的一种有前途的治疗方法。在这项研究中，我们合成了磷脂酰乙醇胺二棕榈酰-Gb(3) (Gb(3)-PEDP) 和半乳糖基(Gb(2))-PEDP 的单价Stx 配体，并在体外检测了它们对Stx-1 和Stx-2 的中和活性。 Gb,-PEDP 和 Gb,-PEDP 均强烈中和 Stx-1 和 Stx-2 的细胞毒性。中和机制可能涉及脂质体的形成以及因此糖单元的聚集。我们提出与磷脂酰残基缀合的单价 Gb(3)-/Gb(2)-衍生物作为一类新型 Stx 中和剂。
Shiga toxin (Stx) exerts toxic activity by binding to glycosphingolipids, mainly globotriaosyl (Gb(3)) 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-Gb(3) (Gb(3)-PEDP) and galabiosyl (Gb(2))-PEDP and we examined their neutralizing activity against Stx-1 and Stx-2 in vitro. Both Gb,-PEDP and Gb,-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 Gb(3)-/Gb(2)-derivatives conjugated with phosphatidyll residue as a novel class of Stx-neutralizing agent.