Sarkar A K, Brown J R, Esko J D
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093, USA.
Carbohydr Res. 2000 Nov 3;329(2):287-300. doi: 10.1016/s0008-6215(00)00200-7.
Five disaccharides related in structure to the glycans of vertebrate mucins have been chemically synthesized using orthogonal blocking, coupling and deblocking techniques. These include 2-naphthylmethyl 3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-( 1 --> 4)-2-acetamido-3,6-di-O-acetyl-2-deoxy-beta-D-glucopyranoside (6), 2-naphthylmethyl 2-aceta-mido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1 --> 3)-2,4,6-tri-O-acetyl-beta-D-galactopyranoside (14), 2-naph-thylmethyl2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-(1 --> 3)-2-acetamido-4,6-di- O-acetyl-2-deoxy-alpha-D-galactopyranoside (20), 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1 --> 3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside (23) and 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glu-copyranosyl-(1 --> 6)-2-acetamido-3,4-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside (27). These per-O-acetylated compounds were fed to U-937 cells to test their ability to prime oligosaccharide synthesis, inhibit glycoprotein biosynthesis and alter adhesion to E-selectin expressed on endothelial cells. The results show that 6, 14, and 20 served as substrates for oligosaccharide synthesis. The generation of glycoside-primed glycans altered the formation of glycoproteins on the cell surface and inhibited cell adhesion dependent on E-selectin.
已使用正交保护、偶联和脱保护技术化学合成了五种结构上与脊椎动物粘蛋白聚糖相关的二糖。这些包括2-萘甲基3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基-(1→4)-2-乙酰氨基-3,6-二-O-乙酰基-2-脱氧-β-D-吡喃葡萄糖苷(6)、2-萘甲基2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-β-D-吡喃葡萄糖基-(1→3)-2,4,6-三-O-乙酰基-β-D-吡喃半乳糖苷(14)、2-萘甲基2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基-(1→3)-2-乙酰氨基-4,6-二-O-乙酰基-2-脱氧-α-D-吡喃半乳糖苷(20)、2-萘甲基2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-β-D-吡喃葡萄糖基-(1→3)-2-乙酰氨基-4,6-二-O-乙酰基-2-脱氧-α-D-吡喃半乳糖苷(23)和2-萘甲基2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-β-D-吡喃葡萄糖基-(1→6)-2-乙酰氨基-3,4-二-O-乙酰基-2-脱氧-α-D-吡喃半乳糖苷(27)。将这些全-O-乙酰化化合物加入U-937细胞中，以测试它们引发寡糖合成、抑制糖蛋白生物合成以及改变对内皮细胞上表达的E-选择素的粘附的能力。结果表明，6、14和20作为寡糖合成的底物。糖苷引发的聚糖的产生改变了细胞表面糖蛋白的形成，并抑制了依赖E-选择素的细胞粘附。
