A new molecule-making machine could do for chemistry what 3D printing did for engineering. It could 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. It would basically be like a 3D printer at the molecular level. In addition, the automated process has the potential to greatly speed up and enable new drug development. Other technologies that rely on small molecules can also improve.
“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.”
The researchers described the technology in a paper featured on the cover of the March 13 issue of Science.
What are small molecules
“Small molecules” are a specific class of complex, compact chemical structures found throughout nature. For that reason, they are very important in medicine and in biology as it uncovers the inner workings of cells and tissues. Most medications available now are small molecules. Small molecules also are key elements in technologies like solar cells and LEDs.
However, small molecules are notoriously difficult to make in a lab. Traditionally, an experienced chemist spends years figuring out how to make each one before its function can even be explored. Such a slowdown hinders the development of small-molecule-based medications and technologies.
“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.”
The main question that Burke’s group seeks to answer: How do you take something very complex and make it as simple as possible?
The strategy
The group’s strategy 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 process is similar with a child interconnecting plastic blocks that have different shapes but snap all together. Many of the building blocks Burke’s lab has developed are available commercially.
University of Illinois chemistry professor Martin Burke explains what a ”3D printer for chemicals” does. He goes on and says that it can assemble complex small molecules from chemical building blocks. This could aid in rapid drug development.
To automate the building-block assembly, Burke’s group devised a simple catch-and-release method. It 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. Also, they are using the same automated building-block assembly.
“Dr. Burke’s research has yielded a significant advance that helps make complex small molecule synthesis more efficient, flexible and accessible,” said Miles Fabian of the National Institutes of Health’s National Institute of General Medical Sciences which partially funded the research. “It is exciting to think about the impact that continued advances in these directions will have on synthetic chemistry and life science research.”
Success is on its way
The automated synthesis technology has been licensed to REVOLUTION Medicines, Inc., a company that Burke co-founded that focuses on creating new medicines based on small molecules found in nature. In addition, the company initially is 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 road map to a general and automated way to make most small molecules. Therefore, 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.
Source: Illinois University
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