Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
J Am Chem Soc. 2010 Mar 24;132(11):3658-9. doi: 10.1021/ja910903c.
We reported recently that certain beta-peptides self-assemble spontaneously into cooperatively folded bundles whose kinetic and thermodynamic metrics mirror those of natural helix bundle proteins. The structures of four such beta-peptide bundles are known in atomic detail. These structures reveal a solvent-sequestered, hydrophobic core stabilized by a unique arrangement of leucine side chains and backbone methylene groups. Here we report that this hydrophobic core can be re-engineered to contain a fluorous subdomain while maintaining the characteristic beta-peptide bundle fold. Like alpha-helical bundles possessing fluorous cores, fluorous beta-peptide bundles are stabilized relative to hydrocarbon analogues and undergo cold denaturation. Beta-peptide bundles with fluorous cores represent the essential first step in the synthesis of orthogonal protein assemblies that can sequester selectively in an interstitial membrane environment.
我们最近报道称，某些β-肽会自发地自组装成协同折叠的束，其动力学和热力学指标与天然螺旋束蛋白的动力学和热力学指标相匹配。这四种β-肽束的结构在原子水平上是已知的。这些结构揭示了一个被溶剂隔离的疏水性核心，由独特的亮氨酸侧链和主链亚甲基的排列稳定。在这里，我们报告说可以对这个疏水性核心进行重新设计，使其包含一个全氟亚基，同时保持特征性的β-肽束折叠。与具有全氟核心的α-螺旋束一样，全氟β-肽束相对于碳氢化合物类似物是稳定的，并且经历冷变性。具有全氟核心的β-肽束是合成可以选择性地在间质膜环境中隔离的正交蛋白质组装体的必要的第一步。
