Sundgren Andreas, Barchi Joseph J
Laboratory of Medicinal Chemistry and, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Carbohydr Res. 2008 Jul 21;343(10-11):1594-604. doi: 10.1016/j.carres.2008.05.003. Epub 2008 May 8.
Three-dimensional self-assembled monolayers of gold coated with the Thomsen-Friedenreich antigen (TF(ag)) disaccharide (beta-Galp-(1-->3)-GalpNAc) in a variety of presentations have been prepared and characterized. Anomalies in the size distribution of our originally synthesized TF(ag)-bearing nanoparticles as shown in dynamic light scattering experiments prompted us to explore the effect of antigen density on the uniformity of the particles. Gold nanoparticles containing a range of densities 'diluted' with copies of the PEG-thiol spacer unit showed that lower antigen density affords more uniform particles. We also wanted to study the constitution of the actual antigen by synthesizing nanoparticles not only with the linker-extended disaccharide, but also within the context of the surrounding peptide sequence where it may be presented in vivo. The synthesis of TF(ag)-containing glycopeptide thiols based on a mucin peptide repeating unit were prepared, assembled into gold nanoparticles and their physical properties evaluated. These novel multivalent tools should prove extremely useful in exploring the binding properties and immune response to this important carbohydrate antigen.
已经制备并表征了用汤姆森-弗里德赖希抗原（TF(ag)）二糖（β-Galp-(1→3)-GalpNAc）以多种形式包覆金的三维自组装单层。动态光散射实验显示，我们最初合成的含TF(ag)纳米颗粒的尺寸分布存在异常，这促使我们探究抗原密度对颗粒均匀性的影响。用聚乙二醇-硫醇间隔单元的拷贝“稀释”一系列密度的金纳米颗粒表明，较低的抗原密度能提供更均匀的颗粒。我们还想通过不仅合成带有连接子延伸二糖的纳米颗粒，而且在其可能在体内呈现的周围肽序列的背景下合成纳米颗粒，来研究实际抗原的组成。基于粘蛋白肽重复单元制备了含TF(ag)的糖肽硫醇，将其组装成金纳米颗粒并评估其物理性质。这些新型多价工具在探索对这种重要碳水化合物抗原的结合特性和免疫反应方面应会被证明极其有用。
