Translational Research Center for Protein Function Control and Department of Materials Science and Engineering, Yonsei University, Seoul 120-749, Korea.
Biomacromolecules. 2013 May 13;14(5):1594-9. doi: 10.1021/bm400233x. Epub 2013 Apr 3.
The stabilization of peptide's active conformation is a critical determinant of its target binding efficiency. Here we present a structure-based self-assembly strategy for the design of nanostructures with multiple and thermostable α-helices using bioinspired peptide amphiphiles. The design principle was inspired by the oligomerization of the human immunodeficiency virus type-1 (HIV-1) Rev protein. Our goal was to find a strategy to modify the Rev protein into a chemically manageable self-assembling peptide while stabilizing its α-helical structure. Instead of using cyclic peptides for structure stabilization, this strategy utilizes the pseudocyclization for helix stabilization. The self-assembly induced stabilization of α-helical conformation could be observed, and the α-helices were found to be stable even at high temperature (at least up to 74 °C). Conjugation of a hydrophobic alkyl chain to the Rev peptide was crucial for forming the self-assembled nanostructures, and no nanostructures could be obtained without this modification. Because chemical modifications to the α-helical peptide domain can be avoided, potentially any α-helical peptide fragment can be grafted into this self-assembling peptide scaffold.
肽的活性构象的稳定是其靶标结合效率的关键决定因素。在这里，我们提出了一种基于结构的自组装策略，用于使用基于生物灵感的肽两亲物设计具有多个热稳定α-螺旋的纳米结构。设计原理受到人类免疫缺陷病毒 1 型 (HIV-1) Rev 蛋白聚合的启发。我们的目标是找到一种将 Rev 蛋白修饰成可化学处理的自组装肽的策略，同时稳定其α-螺旋结构。该策略不使用环状肽来稳定结构，而是利用假环化来稳定螺旋。可以观察到自组装诱导的α-螺旋构象的稳定，并且即使在高温下（至少高达 74°C），α-螺旋也被发现是稳定的。将疏水性烷基链连接到 Rev 肽上对于形成自组装纳米结构至关重要，如果没有这种修饰，则无法获得纳米结构。由于可以避免对α-螺旋肽结构域进行化学修饰，因此任何α-螺旋肽片段都可以嫁接到这种自组装肽支架上。
