School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
J Mol Model. 2011 Aug;17(8):2051-60. doi: 10.1007/s00894-010-0907-1. Epub 2010 Dec 15.
The partial modification of carboxylic acid terminated polyamidoamine (PAMAM) dendrimers with glucosamine has been reported to give dendrimer glucosamine conjugates novel immuno-modulatory and anti-angiogenic properties. Experimental analysis of these glycosylated dendrimers showed that, on average, eight glucosamine molecules were covalently bound to each dendrimer. In order to better understand the surface loading and distribution of these glucosamine molecules, molecular reactivity was determined by evaluation of electronic properties using frontier molecular orbital theory (FMOT) and molecular dynamics simulations. It was shown that the surface loading and distribution of zero length amide bond-conjugated glucosamine molecules was determined by both electronic effects and by the different dynamic conformations adopted by the modified dendrimer during the incremental addition of glucosamine. Importantly, the structural features and the dynamic behavior of the partially glycosylated generation 3.5 PAMAM dendrimer showed that its flexibility and polarity changed with the incremental addition of glucosamine. These peripheral glucosamine molecules remained available on the dendrimer's surface for interaction with the biological target.
已报道用葡糖胺对端羧基聚酰胺-胺（PAMAM）树枝状大分子进行部分修饰，得到具有新型免疫调节和抗血管生成特性的树枝状大分子葡糖胺缀合物。对这些糖基化树枝状大分子的实验分析表明，平均每个树枝状大分子上共价结合了 8 个葡糖胺分子。为了更好地了解这些葡糖胺分子的表面负载和分布，通过使用前沿分子轨道理论（FMOT）和分子动力学模拟评估电子性质来确定分子反应性。结果表明，零长度酰胺键连接的葡糖胺分子的表面负载和分布取决于电子效应以及在葡糖胺的逐步添加过程中修饰的树枝状大分子所采用的不同动态构象。重要的是，部分糖基化第三代 3.5 PAMAM 树枝状大分子的结构特征和动态行为表明，其灵活性和极性随葡糖胺的逐步添加而变化。这些外围的葡糖胺分子仍然可以在树枝状大分子的表面上与生物靶标相互作用。
