Department of Chemistry, Kansas State University, Manhattan, KS, USA.
Department of Anatomy & Physiology, Kansas State University, Manhattan, KS, USA.
Nanomedicine. 2017 Nov;13(8):2555-2564. doi: 10.1016/j.nano.2017.07.004. Epub 2017 Jul 25.
A novel type of supramolecular aggregate, named a "nanosponge" was synthesized through the interaction of novel supramolecular building blocks with trigonal geometry. The cholesterol-(K/D)DEVDGC)-trimaleimide unit consists of a trigonal maleimide linker to which homopeptides (either K or D) of variable lengths (n=5, 10, 15, 20) and a consensus sequence for executioner caspases (DEVDGC) are added via Michael addition. Upon mixing in aqueous buffer cholesterol-(K)DEVDGC)-trimaleimides and a 1:1 mixture of cholesterol-(K/D)DEVDGC)-trimaleimides form stable nanosponges, whereas cholesterol-(D)DEVDGC)-trimaleimide is unable to form supramolecular aggregates with itself. The structure of the novel nanosponges was investigated through explicit solvent and then coarse-grained molecular dynamics (MD) simulations. The nanosponges are between 80 nm and several micrometers in diameters and virtually non-toxic to monocyte/macrophage-like cells.
通过新型超分子构筑基元与三角几何的相互作用，合成了一种新型的超分子聚集体，称为“纳米海绵”。胆固醇-（K/D）DEVDGC）-三马来酰亚胺单元由一个三角马来酰亚胺连接子组成，通过迈克尔加成将同聚肽（K 或 D）的不同长度（n=5、10、15、20）和执行 caspase 的共有序列（DEVDGC）添加到其中。在水缓冲液中混合时，胆固醇-（K）DEVDGC）-三马来酰亚胺和胆固醇-（K/D）DEVDGC）-三马来酰亚胺的 1:1 混合物形成稳定的纳米海绵，而胆固醇-（D）DEVDGC）-三马来酰亚胺本身无法形成超分子聚集体。通过显式溶剂和粗粒分子动力学（MD）模拟研究了新型纳米海绵的结构。纳米海绵的直径在 80nm 到数微米之间，对单核细胞/巨噬细胞样细胞几乎没有毒性。
