Monovalent Gb3-/Gb2-derivatives conjugated with a phosphatidyl residue: a novel class of Shiga toxin-neutralizing agent.
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(3)-PEDP and Gb(2)-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 phosphatidyl residue as a novel class of Stx-neutralizing agent.
Neri
Paola
P
Laboratory of Microbiology, Department of Public Health Pharmacy, Gifu Pharmaceutical University, Gifu 502-8585, Japan.
Tokoro
Shunji
S
Yokoyama
Shin-Ichiro
S
Miura
Tsuyoshi
T
Murata
Takeomi
T
Nishida
Yoshihiro
Y
Kajimoto
Tetsuya
T
Tsujino
Satoshi
S
Inazu
Toshiyuki
T
Usui
Taiichi
T
Mori
Hiroshi
H
D002240:Carbohydrate Sequence; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D005915:Globosides / Q000138:chemical synthesis / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry*; D022621:Shiga Toxin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D022622:Shiga Toxin 1 / Q000037:antagonists & inhibitors / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors / Q000633:toxicity; D014281:Trihexosylceramides / Q000138:chemical synthesis / Q000494:pharmacology*