title: Synthesis of a Candida albicans tetrasaccharide spanning the β1,2-mannan phosphodiester α-mannan junction.
abstract: The cell wall phosphomannan of Candida species is a complex N-linked glycoprotein with a glycan chain containing predominantly an α-linked mannose backbone with α-mannose branches. A minor β-mannan component is attached to the branches either via a glycosidic bond (acid stable β-mannan) or a phosphodiester bond (acid-labile β-mannan). The α-mannan residues of the cell wall phosphomannan do not afford protective antibody, while the β-mannan portion is a protective antigen and has become an attractive target as the key epitope of a conjugate vaccine. We report the first synthesis of a tetrasaccharide 1 consisting of a β1,2-mannopyranosyl trisaccharide linked via a phosphodiester to methyl α-mannopyranoside. This encompasses the attachment site of the acid labile β-mannan to the α-mannan component of the cell wall phosphomannan. The trisaccharide was formed by an iterative process to first create a β-glucopyranoside linkage and then epimerize the C-2 center via an oxidation-reduction sequence. The phosphate diester linkage was accessed via an anomeric H-phosphonate. The binding of phosphomannan fragment 1 with the protective antibody C3.1 has been evaluated and compared with a β-mannotrioside in hapten inhibition experiments. The observed activities are rationalized with a model for docked in the binding site of C3.1.
authors.affiliation: Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: Anh-Thu
authors.initials: AT
authors.lastname: Dang
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
authors.forename: David R
authors.initials: DR
authors.lastname: Bundle
mesh_terms: D002176:Candida albicans / Q000737:chemistry*; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000737:chemistry; D008351:Mannans / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry*; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000939:Epitopes; D008351:Mannans; D009841:Oligonucleotides; D011134:Polysaccharides; C116746:phosphodiester alpha; C005437:phosphomannan