Molecular Machines made from Lasso Peptides

纳米技术的一个基本概念是功能系统的小型化，例如分子机器的建造和它们在纳米尺度上的操作。机械互锁的分子，如轮烷或环戊二烯，是合成分子机器的很有前途的原型。随着2016年诺贝尔化学奖被授予该领域，这项研究被推入了普通公众的视野。然而，生物相容性的缺乏和具有挑战性的多步骤合成使这些合成纳米设备的应用变得复杂。有前景的合成系统的替代品是具有机械互锁结构的天然产品，如套索多肽。它们缠绕在一起的结构可以很容易地通过化学和生物化学工具进行操作，这使得它们可以转化为轮烷和链烷。此外，一些套索多肽可以发生可逆的构象变化，这使得它们适合作为分子开关。在这个项目中，将构建适合作为分子机器使用的新型多肽结构。在第一步中，套索多肽将被化学修饰，以实现分子间的连接。利用这些修饰的多肽构建块进行分子自组装将随后产生更复杂的链烷。通过合理的设计，可以在产生的机械互锁分子中产生受控的分子运动。因此，基于套索的多肽系统提供了一种在很大程度上未被探索的，但很有希望的合成分子机器的替代品。

A fundamental idea of nanotechnology is the miniaturization of functional systems, e.g. the construction of molecular machines and their operation at the nanoscale. Mechanically interlocked molecules such as rotaxanes or catenanes are promising prototypes for synthetic molecular machines. With the awarding the Nobel Prize in Chemistry to this field in 2016, this research has been pushed into the view of the general public. However, the lack of biocompatibility and challenging multi-step synthesis complicate applications of these synthetic nanodevices. Promising alternatives to synthetic systems are natural products with mechanically interlocked structures such as lasso peptides. Their intertwined structure can be easily manipulated by tools of chemistry and biochemistry, which allows a conversion into rotaxanes and catenanes. Additionally, some lasso peptides can undergo reversible conformational changes, which make them suitable as molecular switches. In this project, novel peptide-based architectures will be constructed suitable for the use as molecular machines. In a first step, lasso peptides will be chemically modified to enable intermolecular linkage. Molecular self-assembly utilizing these modified peptide building blocks will subsequently lead to more complex catenanes. Through a rational design controlled molecular motion can be generated in the resulting mechanically interlocked molecules. Thus, lasso peptide-based systems offer a largely unexplored, yet promising alternative to synthetic molecular machines.