Unidad de Biofisica, Centro Mixto CSIC-UPV/EHU, Universidad del Pais Vasco, 48080 Bilbao, Spain.
Bioconjug Chem. 2010 Jul 21;21(7):1280-7. doi: 10.1021/bc100079n.
Oligonucleotide conjugates carrying carbohydrates at the 5'-end have been prepared. Glucose, fucose, and saccharides containing glucose at the nonreducing end were attached to DNA strands using the classical phosphoramidite chemistry. Two types of spacers and a dendron scaffold helped to obtain a diversity of sugar presentations in the DNA conjugates. Cellular surface adsorption and cellular uptake of carbohydrate oligonucleotide antisense sequences were measured using flow cytometric analysis. Conjugates with the glucose moiety linked through long spacers (15 to 18 atom distances) were internalized better than those with short linkers (4 atom distance) and than DNA control strands without sugar modification. Conjugates with tetravalent presentation of glucose did not improve cell uptake.
已制备了在 5'端带有碳水化合物的寡核苷酸缀合物。使用经典的亚磷酰胺化学将葡萄糖、岩藻糖和非还原端含有葡萄糖的糖连接到 DNA 链上。两种类型的间隔物和树突状支架有助于在 DNA 缀合物中获得多种糖呈现形式。使用流式细胞术分析测量了细胞表面吸附和细胞摄取碳水化合物寡核苷酸反义序列。通过长间隔物（15 至 18 个原子距离）连接的葡萄糖部分缀合物比具有短接头（4 个原子距离）和没有糖修饰的 DNA 对照链更容易被内化。具有四价葡萄糖呈现形式的缀合物不会改善细胞摄取。
