Researchers at ETH Zurich announced on Mar. 10 a new chemical method that enables the synthesis of poorly soluble proteins by using a reactive boron compound. The development could lead to advances in the production of protein therapeutics, including those used for cancer treatment.
Many important proteins in medicine and science are difficult to produce because they tend to clump together when their concentration rises, making them insoluble and nonfunctional. This has posed a challenge for chemists, as current laboratory methods require high concentrations of protein fragments to successfully join them into complete proteins.
The team led by Jeffrey Bode, professor at the Laboratory of Organic Chemistry at ETH Zurich, addressed this issue by introducing boron atoms into carbon-based molecules. This approach accelerates the coupling reaction between protein segments, allowing it to occur at much lower concentrations—about 1,000 times lower than conventional methods. "This kind of fundamental research, where we can venture into uncharted scientific territory with no guarantee of success, is only possible thanks to unrestricted funds from the Swiss National Science Foundation and ETH," Bode said.
The breakthrough came after years of unsuccessful attempts to stabilize the sensitive boron compound needed for automated synthesis. A doctoral student discovered a protective chemical packaging that shields the boron group from acids during protein production. This innovation now allows standard laboratory robots to produce peptide and protein medications or membrane proteins prone to clumping.
The new method also enables chemists to introduce unnatural amino acids with special properties into specific positions on poorly soluble proteins. This capability is useful for creating antibody–drug conjugates used in targeted cancer therapies that minimize harm to healthy tissue.
While it remains uncertain how quickly this technique will be adopted in clinical practice, Bode cofounded Bright Peak Therapeutics in 2020—a company developing immunotherapies based on his group's technologies. An initial therapeutic agent is already undergoing clinical trials, and the new boron-based approach may help expand future treatment options.
