Related Experiment Videos
Fucosyltransferases in Schistosoma mansoni development
E T Marques1, Y Ichikawa, M Strand
1Department of Pharmacology and Molecular Sciences and Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Glycobiology
|April 26, 2001
Summary
Schistosome parasites show high fucosyltransferase activity in eggs, with specific enzymes modifying various oligosaccharides. A novel iminosugar inhibitor effectively blocked a key fucosylated antigen linked to disease pathogenesis.
Area of Science:
- Biochemistry
- Parasitology
- Glycobiology
Background:
- Fucose is abundant in Schistosoma mansoni glycoconjugates, with diverse linkage types identified.
- Fucosyltransferases play a crucial role in synthesizing these fucosylated structures.
Purpose of the Study:
- To quantify fucosyltransferase activities across different developmental stages of S. mansoni.
- To characterize the substrate specificity of schistosome fucosyltransferases.
- To evaluate the inhibitory potential of fucose-type iminosugars against schistosome fucosyltransferases.
Main Methods:
- Assays utilized fluorophore-assisted carbohydrate electrophoresis.
- Radioactive fucose incorporation from GDP-\[(14)C\-fucose] was detected.
- Substrate specificity was assessed using structurally defined oligosaccharide acceptors.
Main Results:
- Egg extracts exhibited 50-fold higher total fucosyltransferase activity compared to cercaria and adult worms.
- Identified fucosyltransferases acting on type-2, type-1, and lactose-based oligosaccharides, including multifucosylated products.
- A novel 1-N-iminosugar demonstrated 4-6 fold greater inhibitory potency than deoxyfuconojirimycin in vitro and blocked a pathogenic fucosylated epitope in vivo.
Conclusions:
- Fucosyltransferase activity is significantly elevated in S. mansoni eggs.
- Specific fucosyltransferases involved in parasite glycoconjugate synthesis have been characterized.
- A novel iminosugar shows promise as a therapeutic agent by inhibiting a key fucosylated antigen involved in schistosomiasis pathogenesis.