Takahashi Y, Ueno A, Mihara H
Department of Bioengineering, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Bioorg Med Chem. 1999 Jan;7(1):177-85. doi: 10.1016/s0968-0896(98)00236-3.
Recent studies on peptide fibrillogenesis by the de novo method as well as amyloidogenic proteins including prion proteins and Alzheimer's beta-peptides have provided insights into the conformational changes, such as alpha-helix to beta-structure, involved in folding and misfolding processes. We have found that an exposed hydrophobic nucleation domain at N-terminal causes a structural transition of a peptide from alpha-helix to beta-fibril. It became clear that N-terminal acyl groups of particular lengths in a 2alpha-helix peptide caused the peptide to undergo an alpha-to-beta transition. The peptide with the octanoyl group (C8-2alpha) showed the highest rate of transformation. The study of the designed peptides revealed that these alpha-to-beta transitions were closely related to the initial alpha-helix conformation and its stability. Engineering peptides that undergo alpha-to-beta transitions are attractive not only to the study of pathogenic proteins such as prion proteins, but also to the control of self-assembly of peptides, which will lead to the development of peptidyl self-assembling materials.
最近通过从头合成法对肽纤维形成以及包括朊病毒蛋白和阿尔茨海默氏β肽在内的淀粉样蛋白的研究，为折叠和错误折叠过程中涉及的构象变化（如α螺旋到β结构）提供了见解。我们发现，N端暴露的疏水成核结构域会导致肽从α螺旋向β纤维发生结构转变。很明显，2α螺旋肽中特定长度的N端酰基会使肽发生α到β的转变。带有辛酰基（C8 - 2α）的肽显示出最高的转化率。对设计肽的研究表明，这些α到β的转变与初始α螺旋构象及其稳定性密切相关。经历α到β转变的工程肽不仅对研究诸如朊病毒蛋白等致病蛋白具有吸引力，而且对控制肽的自组装也具有吸引力，这将导致肽基自组装材料的开发。
