Neutralizing Activity of Polyvalent Gb3, Gb2 and Galacto‐Trehalose Models against Shiga Toxins

• DOI: 10.1111/j.1348-0421.2007.tb03944.x
• Publication Date: 2013-11-14T14:06:54Z
• Authors: Paola Neri; Saori Itoh Nagano; Shin‐ichiro Yokoyama; Hirofumi Dohi; Kazukiyo Kobayashi; Tsuyoshi Miura; Toshiyuki Inazu; Tsuyoshi Sugiyama; Yoshihiro Nishida; Hiroshi Mori
• Keywords: Shiga-like toxin

Shiga toxin (Stx) is one of the most critical factors in development hemolytic uremic syndrome and other systemic complications following enterohemorrhagic Escherichia coli (EHEC) infection. Substances neutralizing Stx by interfering with toxin-receptor binding have been explored as therapeutic candidates for EHEC In this study, we examined globotriaosyl (Gb3), galabiosyl (Gb2) galacto-trehalose, each which was synthetically conjugated a polyacrylamide backbone, Stxneutralizing activity. Galacto-trehalose designed Gb2 mimicking, unnatural Stx-ligand that expected to show tolerance enzymatic degradation vivo. copolymer showed activity against Stx-1 but not Stx-2 HeLa cell cytotoxicity assay. It thought galactotrehalose could be lead compound treatment Stx-mediated diseases, although it requires modification Stx-2. The Gb3 high sugar unit density stronger than those lower density. However, density-dependency less obvious Stx-1. Intravenous administration prevented death mice lethally infected Stx-1- Stx-2-producing E. O157:H7. Thus, demonstrated artificial neutralize more clinically relevant vitro effectively inhibit toxicity