Chemist Marty Burke from the University of Illinois Urbana-Champaign has developed a way to create a machine that assembles molecules at the touch of a button. In his system, a computer controls a system of pumps and injectors to push solutions containing building blocks that can be linked together like building blocks to create a wide range of larger and more complex molecules.
Assembly of Complex Molecules by Machine
The process of assembling complex molecules is an extremely difficult art – a daily task for many chemists. But Marty Burke, a chemist at the University of Illinois Urbana-Champaign, says he has found a way to create a machine that assembles molecules at the touch of a button.
Assembly of Molecules by Robot
Burke’s machine uses a computer, pumps, and injectors to automatically assemble complex molecules by putting together chemical building blocks. Burke has been working for years on developing important core building blocks, a library of organic acid molecules containing boron, called MIDA boronates. These compounds – now commercially available – are designed to contain chemical groups at each end that can easily react with each other. By assembling the right building blocks in the correct order, Burke has already reported that it is possible to make a wide variety of larger molecules and different shapes.
Machine Achieving Automated Assembly
Typically, using pumps and injectors to move compounds – a process known as “flow chemistry” – is not sufficient for complete control. Usually, there is a need for manual purification after assembling two building blocks: unwanted by-products and impurities must be washed away, and the newly assembled molecule must be successfully retrieved for future reactions with another building block. But Burke’s team has found a way to achieve automatic control over the purification process as well: freshly reactive MIDA boronates adhere to silica gel, making it easy to wash away other chemicals. Then, by adding another solvent called tetrahydrofuran (THF), Burke found it possible to wash MIDA boronates separately for future reactions. “The entire process is carried out from start to finish by the machine,” says Burke.
Iterative Assembly of Molecules
Chemists have influenced the peptide manufacturing process (short chains of proteins made from building blocks of amino acids): the resin holds the growing peptide chain, and unreacted building blocks are simply washed away. However, peptide manufacturing is a much simpler problem to solve: a limited set of amino acid residues are connected together in a straight line. Burke’s diverse building blocks can create complex molecules that contain branches and rings.
Using the Machine for Drug Discovery
Bartosz Grzybowski, a chemist at the National Institute of Science and Technology in Ulsan, South Korea, says Burke’s system would be useful for drug discovery, where large libraries of new molecules are screened for their ability to combat diseases. “It would be great for the pharmaceutical industry,” he says. Although there are 200 commercially available MIDA boronates, Grzybowski wonders whether the appropriate types of assembly will always be available to create a specific molecule of interest.
Development of the Machine and Its Future Use
Burke’s machine may not reach a chemistry lab near you any time soon. The core automation technology has been patented and exclusively licensed to Revolution Medicines in Redwood City, California, which Burke co-founded. Mark Goldsmith, CEO of Revolution, says the next step will be an investment in developing the prototype kit that Burke created in his lab and seeing how it might help them in drug discovery. In the future, Goldsmith says the company may seek partnerships with other collaborators.
References:
Li, J. et al. Science 347, 1221–1226 (2015).
Woerly,
E. M., Roy, J. & Burke, M. D. Nature Chemistry 6 484-491 (2014)
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