Synthesis and immunochemical characterization of S-linked glycoconjugate vaccines against Candida albicans.
Replacement of the glycosidic oxygen atom by a sulphur atom is a promising technique for creating glycoconjugates with increased resistance to hydrolysis by endogenous glycosidases. The synthesis and antigenic properties of two distinct (1-->2)-beta-mannan trisaccharides with inter residue-S-linked mannopyranose residues are described. Syntheses were based on an oxidation-reduction strategy to construct the O-linked beta-mannopyranoside bonds and a SN2 inversion to provide 1-thio-beta-mannopyranoside residues. Subsequently the allyl trisaccharide glycosides were subjected to photo addition with cysteine amine and coupled to tetanus toxoid and bovine serum albumin with good efficiency via an adipic acid tether. Rabbit immunization studies revealed that the antibodies elicited by the two glycoconjugates were able to recognize the corresponding O-linked trisaccharide epitope conjugated to BSA and the native cell wall antigen of Candida albicans.
Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
Xiangyang
X
Wu
Tomasz
T
Lipinski
Eugenia
E
Paszkiewicz
David R
DR
Bundle
D000081:Acetamides; D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D062845:Chloroacetates; D004952:Esters / Q000737:chemistry; D005657:Fungal Vaccines / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*; D006023:Glycoproteins / Q000737:chemistry; D006031:Glycosylation; D007114:Immunization; D007120:Immunochemistry; D008358:Mannose / Q000737:chemistry; D010084:Oxidation-Reduction; D011817:Rabbits; D014238:Trichloroacetic Acid / Q000737:chemistry; D014312:Trisaccharides / Q000737:chemistry
D000081:Acetamides; D062845:Chloroacetates; D004952:Esters; D005657:Fungal Vaccines; D006001:Glycoconjugates; D006023:Glycoproteins; D014312:Trisaccharides; D014238:Trichloroacetic Acid; C009528:trichloroacetamide; D008358:Mannose