Molecular Machines made from Lasso Peptides

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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.