Université de Bordeaux , CBMN, UMR 5248, Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac, France.
CNRS , CBMN, UMR 5248, 33600, Pessac, France.
J Am Chem Soc. 2016 Aug 24;138(33):10522-30. doi: 10.1021/jacs.6b05063. Epub 2016 Aug 15.
Non-natural synthetic oligomers that adopt well-defined secondary structures (i.e., foldamers) represent appealing components for the fabrication of bioinspired self-assembled architectures at the nanometer scale. Recently, peptidomimetic N,N'-linked oligourea helices have been designed de novo with the ability to fold into discrete helix bundles in aqueous conditions. In order to gain better insight into the determinants of oligourea helix bundle formation, we have investigated the sequence-to-structure relationship of an 11-mer oligourea previously shown to assemble into a six-helix bundle. Using circular dichroism, NMR spectroscopy, native mass-spectrometry and X-ray crystallography, we studied how bundle formation was affected by systematic replacement of the hydrophobic surface of the oligourea helix with either polar or different hydrophobic side chains. The molecular information gathered here has revealed several key requirements for foldamer bundle formation in aqueous conditions, and provides valuable insight toward the development of foldamer quaternary assemblies with improved (bio)physical properties and divergent topologies.
非天然合成的寡聚物采用明确的二级结构（即折叠体），是在纳米尺度上制造仿生自组装结构的有吸引力的组成部分。最近，具有在水相条件下折叠成离散螺旋束的能力的肽模拟 N，N'-连接的寡脲螺旋体已被从头设计。为了更好地了解寡脲螺旋体束形成的决定因素，我们研究了以前显示组装成六螺旋体束的 11 元寡脲的序列-结构关系。使用圆二色性，NMR 光谱，天然质谱和 X 射线晶体学，我们研究了系统地用极性或不同疏水性侧链取代寡脲螺旋体的疏水性表面如何影响束的形成。这里收集的分子信息揭示了在水相条件下折叠体束形成的几个关键要求，并为具有改进的（生物）物理性质和不同拓扑结构的折叠体四级组装的发展提供了有价值的见解。
