Artificial Molecular Machines in Biosystems

Molecular machines are used by Nature in almost every conceivable biological task, and during the last decades construction of artificial molecular machinery has also blossomed into a prospering research field. However, the merging of synthetic machines with biological applications is nearly completely unexplored.

Herein, I propose the use of artificial molecular machines to control biological interactions.

Specifically, I want to design, synthesize and investigate synthetic molecular machines that can interact with proteins and other biomolecules.Initially, I propose methods to operate and analyse synthetic molecular machinery in biological settings, using tools such as dynamic covalent chemistry and luminescent lanthanide reporters.

Next, molecular [2]rotaxanes shuttles will be eployed as diagnostic biosensors that use molecular movement to report on specific protein targets.

Finally, I will create novel machine-drug conjugates, a form of “smart therapeutics” where biological activity can be switched on or off on command.The project will be conducted over four years and is focused on organic synthesis of the machines and analysis of their operation. Collaborations to study all details of the molecules have been established.

This work will show how cutting-edge nanoscale synthetic molecular machinery can be employed to solve otherwise insurmountable challenges in chemical biology, and open a route to drugs and diagnostics with less side effects and higher specificity.