Mendoza Verónica M, Agusti Rosalía, Gallo-Rodriguez Carola, de Lederkremer Rosa M
CIHIDECAR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires, Argentina.
Carbohydr Res. 2006 Jul 24;341(10):1488-97. doi: 10.1016/j.carres.2006.03.033. Epub 2006 Apr 21.
The mucin-like glycoproteins of Trypanosoma cruzi have novel O-linked oligosaccharides that are acceptors of sialic acid in the trans-sialidase (TcTS) reaction. The transference of sialic acid from host glycoconjugates to the mucins is involved in infection and pathogenesis. The synthesis of the pentasaccharide, beta-D-Galp-(1-->2)-[beta-D-Galp-(1-->3)]-beta-D-Galp-(1-->6)-[beta-D-Galf-(1-->4)]-D-GlcpNAc and the corresponding alditol, previously isolated by reductive beta-elimination of the mucins, is described. The key step was the 6-O-glycosylation of a easily accessible derivative of beta-D-Galf-(1-->4)-D-GlcpNAc with a beta-D-Galp-(1-->2)-[beta-D-Galp-(1-->3)]-D-Galp donor using the trichloroacetimidate method. The beta-linkage was diastereoselectively obtained by the nitrile effect. The pentasaccharide is the major oligosaccharide in the mucins of T. cruzi, G strain and presents two terminal beta-D-Galp residues for possible sialylation by TcTS. A preparative sialylation reaction was performed with its benzyl glycoside and the sialylated product was isolated and characterized. NMR spectroscopic analysis showed that selective monosialylation occurred at the terminal (1-->3) linked galactopyranose.
克氏锥虫的黏蛋白样糖蛋白具有新型的 O-连接寡糖，它们是转唾液酸酶（TcTS）反应中唾液酸的受体。唾液酸从宿主糖缀合物转移至黏蛋白参与了感染和发病机制。本文描述了通过对黏蛋白进行还原性β-消除先前分离得到的五糖β-D-吡喃半乳糖-(1→2)-[β-D-吡喃半乳糖-(1→3)]-β-D-吡喃半乳糖-(1→6)-[β-D-呋喃半乳糖-(1→4)]-D-乙酰氨基葡萄糖及其相应糖醇的合成。关键步骤是使用三氯乙酰亚胺酯法，将β-D-呋喃半乳糖-(1→4)-D-乙酰氨基葡萄糖的一种易于获得的衍生物与β-D-吡喃半乳糖-(1→2)-[β-D-吡喃半乳糖-(1→3)]-D-吡喃半乳糖供体进行 6-O-糖基化反应。通过腈效应非对映选择性地获得β-连接。该五糖是克氏锥虫 G 株黏蛋白中的主要寡糖，具有两个末端β-D-吡喃半乳糖残基，可被 TcTS 进行唾液酸化。用其苄基糖苷进行了制备性唾液酸化反应，并对唾液酸化产物进行了分离和表征。核磁共振光谱分析表明，选择性单唾液酸化发生在末端（1→3）连接的吡喃半乳糖上。
