Synthesis of a Candida albicans tetrasaccharide spanning the β1,2-mannan phosphodiester α-mannan junction
Synthesis of a Candida albicans tetrasaccharide spanning the β1,2-mannan phosphodiester α-mannan junction
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DOI：
10.1039/c2ob26355f
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发表时间：
2012-01-01
影响因子：
3.2
通讯作者：
Bundle, David R.
中科院分区：
文献类型：
--
作者：
Dang, Anh-Thu;Johnson, Margaret A.;Bundle, David R.
念珠菌属的细胞壁磷酸甘露聚糖是一种复杂的 N-连接糖蛋白，其聚糖链主要包含具有 α-甘露糖分支的 α-连接甘露糖主链。少量β-甘露聚糖成分通过糖苷键（酸稳定的β-甘露聚糖）或磷酸二酯键（酸不稳定的β-甘露聚糖）连接到分支上。细胞壁磷酸甘露聚糖的α-甘露聚糖残基不提供保护性抗体，而β-甘露聚糖部分是保护性抗原，并且已成为作为结合疫苗的关键表位的有吸引力的靶标。我们报道了四糖 1 的首次合成，该四糖 1 由通过磷酸二酯与甲基α-吡喃甘露糖苷连接的 β1,2-吡喃甘露糖基三糖组成。这包括酸不稳定的β-甘露聚糖与细胞壁磷酸甘露聚糖的α-甘露聚糖组分的附着位点。三糖是通过迭代过程形成的，首先创建 β-吡喃葡萄糖苷键，然后通过氧化还原序列使 C-2 中心差向异构化。通过异头 H-膦酸酯连接磷酸二酯键。在半抗原抑制实验中评估了磷酸甘露聚糖片段 1 与保护性抗体 C3.1 的结合并与 β-甘露三苷进行了比较。观察到的活性通过停靠在 C3.1 结合位点的 1 模型进行合理化。
The cell wall phosphomannan of Candida species is a complex N-linked glycoprotein with a glycan chain containing predominantly an alpha-linked mannose backbone with alpha-mannose branches. A minor beta-mannan component is attached to the branches either via a glycosidic bond (acid stable beta-mannan) or a phosphodiester bond (acid-labile beta-mannan). The alpha-mannan residues of the cell wall phosphomannan do not afford protective antibody, while the beta-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 beta 1,2-mannopyranosyl trisaccharide linked via a phosphodiester to methyl a-mannopyranoside. This encompasses the attachment site of the acid labile beta-mannan to the alpha-mannan component of the cell wall phosphomannan. The trisaccharide was formed by an iterative process to first create a beta-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 beta-mannotrioside in hapten inhibition experiments. The observed activities are rationalized with a model for 1 docked in the binding site of C3.1.