Total synthesis of Le(A)-LacNAc pentasaccharide as a ligand for Clostridium difficile toxin A.
The toxins TcdA and TcdB produced by the human pathogen Clostridium difficile gain entrance to host epithelial cells by recognizing cell-surface carbohydrate ligands. Inhibiting the attachment of these toxins to host cells has been proposed to be a viable therapy to treat C. difficile infections. Glycan array screening previously revealed that the Le(A)-LacNAc pentasaccharide binds strongly to TcdA. Here we report the efficient syntheses of the pentasaccharide and a structurally related tetrasaccharide motif. These compounds will be used to better define the carbohydrate-binding specificity of toxins from C. difficile, which will hopefully lead to the development of improved therapeutics.
Zhang
Ping
P
Department of Chemistry, Alberta Ingenuity Center for Carbohydrate Science, University of Calgary, Calgary Alberta, T2N 1N4, Canada.
Ng
Kenneth
K
Ling
Chang-Chun
CC
D001427:Bacterial Toxins / Q000378:metabolism*; D002240:Carbohydrate Sequence; D016360:Clostridioides difficile / Q000378:metabolism*; D004768:Enterotoxins / Q000378:metabolism*; D007983:Lewis Blood Group Antigens; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding
D001427:Bacterial Toxins; D004768:Enterotoxins; D007983:Lewis Blood Group Antigens; C494219:Lewis a oligosaccharide; D008024:Ligands; D009844:Oligosaccharides; C041348:tcdA protein, Clostridium difficile