Department of Chemistry, Brown University , Providence, Rhode Island 02912, United States.
Bioconjug Chem. 2012 Jun 20;23(6):1166-73. doi: 10.1021/bc2006169. Epub 2012 May 16.
The carbohydrates galactose and 3-sulfogalactose, found on sphingolipids in myelin, interact with each other via a carbohydrate-carbohydrate interaction (CCI). In oligodendrocytes, this interaction triggers a signaling cascade resulting in cytoskeletal rearrangements and reorganization of glycolipids and proteins at the cellular surface. These rearrangements can also be triggered by synthetic multivalent glycoconjugates. In this report, we describe the synthesis of glycan-coated silica nanoparticles and their subsequent binding to cultured oligodendrocytes and purified myelin. Fluorescent silica nanoparticles with an azidosiloxane-derived outer shell were functionalized with carbohydrates using the copper-promoted azide-alkyne cycloaddition reaction. The carbohydrate-carbohydrate interaction between galactose and 3-sulfogalactose was examined by measuring the binding of 3-sulfogalactose-containing nanoparticles to galactolipids that had been immobilized in a multiwell plate. Particle aggregation mediated by CCI was observed by TEM. The interaction of the particles with oligodendrocytes and purified myelin was examined using fluorescence microscopy, providing direct evidence for binding of galactose and 3-sulfogalactose-coated nanoparticles to oligodendrocytes and myelin fragments.
鞘糖脂中的半乳糖和 3-硫酸半乳糖通过碳水化合物-碳水化合物相互作用（CCI）相互作用。在少突胶质细胞中，这种相互作用触发信号级联反应，导致细胞骨架重排和细胞表面糖脂和蛋白质的重新排列。这种重排也可以被合成的多价糖缀合物触发。在本报告中，我们描述了糖涂层二氧化硅纳米粒子的合成及其随后与培养的少突胶质细胞和纯化的髓鞘的结合。使用铜促进的叠氮化物-炔烃环加成反应，通过将叠氮硅氧烷衍生的外壳功能化，用碳水化合物功能化具有荧光的硅纳米粒子。通过测量固定在多微孔板中的半乳糖脂与含 3-硫酸半乳糖的纳米粒子的结合，研究了半乳糖和 3-硫酸半乳糖之间的碳水化合物-碳水化合物相互作用。通过 TEM 观察到 CCI 介导的颗粒聚集。使用荧光显微镜检查了颗粒与少突胶质细胞和纯化的髓鞘的相互作用，为半乳糖和 3-硫酸半乳糖涂层纳米粒子与少突胶质细胞和髓鞘片段的结合提供了直接证据。
