A new molecule-making machine could do for chemistry what 3-D printing did for engineering: Make it fast, flexible and accessible to anyone.
Chemists at the University of Illinois, led by chemistry professor and medical doctor Martin D. Burke, built the machine to assemble complex small molecules at the click of a mouse, like a 3-D printer at the molecular level. The automated process has the potential to greatly speed up and enable new drug development and other technologies that rely on small molecules.
"We wanted to take a very complex process, chemical synthesis, and make it simple," said Burke, a Howard Hughes Medical Institute Early Career Scientist. The strategy of Burke’s group has been to break down the complex molecules into smaller building blocks that can be easily assembled. The chemical building blocks all have the same connector piece and can be stitched together with one simple reaction, the way interconnecting plastic blocks can have different shapes but all snap together. Many of the building blocks developed by Burke’s laboratory are available commercially.
To automate the building-block assembly, the group devised a simple catch-and-release method that adds one building block at a time, rinsing the excess away before adding the next one. They demonstrated that their machine can build 14 different classes of small molecules, including ones with difficult-to-manufacture ring structures, all using the same automated building-block assembly.
The automated synthesis technology has been licensed to REVOLUTION Medicines, Inc., a company that Burke co-founded which focuses on creating new medicines based on small molecules found in nature. The company is initially focusing on anti-fungal medications, an area where Burke's research has already made strides.
"It is expected that the technology will similarly create new opportunities in other therapeutic areas as well, as the industrialization of the technology will help refine and broaden its scope and scalability," Burke said. "Perhaps most exciting, this work has opened up an actionable roadmap to a general and automated way to make most small molecules. If that goal can be realized, it will help shift the bottleneck from synthesis to function and bring the power of making small molecules to nonspecialists."