Koga Tomoyuki, Taguchi Kazuhiro, Kobuke Yoshiaki, Kinoshita Takatoshi, Higuchi Masahiro
Nanoarchitectonics Research Center National Institute of Advanced Industrial Science and Technology and CREST (Japan Science and Technology) Tsukuba Central 5, 1-1-1 Higashi, Tsukuba Ibaraki 305-8565, Japan.
Chemistry. 2003 Mar 3;9(5):1146-56. doi: 10.1002/chem.200390132.
The self-assembly of peptides and proteins into beta-sheet-rich high-order structures has attracted much attention as a result of the characteristic nanostructure of these assemblies and because of their association with neurodegenerative diseases. Here we report the structural and conformational properties of a peptide-conjugated graft copolymer, poly(gamma-methyl-L-glutamate) grafted polyallylamine (1) in a water-2,2,2-trifluoroethanol solution as a simple model for amyloid formation. Atomic force microscopy revealed that the globular peptide 1 self-assembles into nonbranching fibrils that are about 4 nm in height under certain conditions. These fibrils are rich in beta-sheets and, similar to authentic amyloid fibrils, bind the amyloidophilic dye Congo red. The secondary and quaternary structures of the peptide 1 can be controlled by manipulating the pH, solution composition, and salt concentration; this indicates that the three-dimensional packing arrangement of peptide chains is the key factor for such fibril formation. Furthermore, the addition of carboxylic acid-terminated poly(ethylene glycol), which interacts with both of amino groups of 1 and hydrophobic PMLG chains, was found to obviously inhibit the alpha-to-beta structural transition for non-assembled peptide 1 and to partially cause a beta-to-alpha structural transition against the 1-assembly in the beta-sheet form. These findings demonstrate that the amyloid fibril formation is not restricted to specific protein sequences but rather is a generic property of peptides. The ability to control the assembled structure of the peptide should provide useful information not only for understanding the amyloid fibril formation, but also for developing novel peptide-based material with well-defined nanostructures.
由于这些聚集体具有独特的纳米结构且与神经退行性疾病相关，肽和蛋白质自组装形成富含β-折叠的高阶结构备受关注。在此，我们报道了一种肽共轭接枝共聚物——聚（γ-甲基-L-谷氨酸）接枝聚烯丙胺（1）在水-2,2,2-三氟乙醇溶液中的结构和构象性质，以此作为淀粉样蛋白形成的简单模型。原子力显微镜显示，球状肽1在特定条件下自组装成高度约为4 nm的无分支纤维。这些纤维富含β-折叠，并且与真正的淀粉样纤维类似，能结合嗜淀粉样染料刚果红。肽1的二级和四级结构可通过调节pH值、溶液组成和盐浓度来控制；这表明肽链的三维堆积排列是这种纤维形成的关键因素。此外，发现添加与1的氨基和疏水性聚甲基-L-谷氨酸链都相互作用的羧酸封端聚乙二醇，能明显抑制未组装肽1从α结构向β结构的转变，并部分导致β结构形式的1组装体发生从β结构向α结构的转变。这些发现表明，淀粉样纤维的形成并不局限于特定的蛋白质序列，而是肽的一种普遍特性。控制肽组装结构的能力不仅应为理解淀粉样纤维的形成提供有用信息，还可为开发具有明确纳米结构的新型肽基材料提供帮助。
