Mechanically interlocked molecules (MIMs), such as rotaxanes and catenanes, have captured the attention of chemists both from a synthetic perspective and because of their role as simple prototypes of molecular machines. Although examples exist in nature, most synthetic MIMs are made from artificial building blocks and assembled in organic solvents. The synthesis of MIMs from natural biomolecules remains highly challenging. Here, we report on a synthesis strategy for interlocked molecules solely made from peptides, that is, mechanically interlocked peptides (MIPs). Fully peptidic, cysteine-decorated building blocks were self-assembled in water to generate disulfide-bonded dynamic combinatorial libraries consisting of multiple different rotaxanes, catenanes and daisy chains as well as more exotic structures. Detailed NMR spectroscopy and mass spectrometry characterization of a [2]catenane comprising two peptide macrocycles revealed that this structure has rich conformational dynamics reminiscent of protein folding. Thus, MIPs can serve as a bridge between fully synthetic MIMs and those found in nature.

机械联锁分子 (MIM)，例如轮烷和链烷，从合成的角度和作为分子机器的简单原型的作用引起了化学家的注意。尽管自然界中存在示例，但大多数合成 MIM 都是由人工构建块制成并在有机溶剂中组装而成。从天然生物分子合成 MIM 仍然极具挑战性。在这里，我们报告了仅由肽制成的互锁分子的合成策略，即机械互锁肽 (MIP)。完全肽、半胱氨酸修饰的结构单元在水中自组装以生成由多种不同轮烷、链烷和菊花链以及更多奇特结构组成的二硫键动态组合文库。包含两个肽大环的 [2] 链烷的详细 NMR 光谱和质谱表征表明，这种结构具有丰富的构象动力学，让人联想到蛋白质折叠。因此，MIP 可以作为完全合成的 MIM 和自然界中发现的 MIM 之间的桥梁。