A new molecule-making machine has been created by chemists at the University of Illinois. The machine could do for chemistry what 3D printing does for engineering, allowing people to make complex small molecules fast, flexible, and accessible to anyone.
Led by chemistry professor and medical doctor Martin D. Burke, chemists at the University of Illinois built the machine to assemble complex small molecules at the click of a mouse. The automated process has the potential to greatly speed up and enable new drug development and other technologies that rely on small carbon-based 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. “Simplicity enables automation, which, in turn, can broadly enable discovery and bring the substantial power of making molecules to nonspecialists.”
Small molecules are notoriously difficult to make in a lab. The process to synthesise small molecules is time-consuming and has to be customised for each application, so researching and creating new drugs currently takes many years, even for highly trained chemists, and a lot of trial and error.
“Up to now, the bottleneck has been synthesis,” Burke said. “There are many areas where progress is being slowed, and many molecules that pharmaceutical companies aren’t even working on, because the barrier to synthesis is so high.”
Looking at the structures of all of the known naturally occurring polyenes, thousands in all, Burke and graduate students Eric Woerly and Jahnabi Roy focused on the smaller pieces that made up the molecules. After careful analysis, they calculated that more than three-quarters of all natural polyene frameworks could be made with just 12 different blocks. The chemists were then successful in synthesizing 14 distinct classes of small molecules from the 12 common set of building blocks.
“That is the key, most surprising, result,” Burke said. “We’ve had this gut instinct that there will be a set number of building blocks from which most natural products can be made. We’re convinced, based on this result, that we can put together a platform that would enable on-demand assembly of complex small molecules. Then researchers can focus on exploring the function of these molecules, rather than spending all their time and energy trying to make them.”
The automated synthesis technology has been licensed to REVOLUTION Mecidines, Inc., a company that Burke co-founded. The company focuses on creating new medicines based on small molecules found in nature, 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.
A wide range of technologies, including LEDs, diagnostic tools and solar cells also rely on small molecules. “Small molecules have already had a big impact on the world,” says Burke. “But we’ve barely touched the surface of what they’re capable of achieving. In large part, that’s because there’s a major synthesis bottleneck that precludes accessing all of their functional potential.”
Burke and his team hope that eventually, anyone could synthesize customized small molecules. “The vision is that anybody could go to a website, pick the building blocks they want, instruct their assembly through the web, and the small molecules would get synthesised and shipped. We’re not there yet, but we now have an actionable roadmap toward on-demand small-molecule synthesis for non-specialists.”