ETH team succeeds in automated production of poorly soluble proteins

Zurich – A team at the Swiss Federal Institute of Technology in Zurich (ETH) has found a way to combine poorly soluble protein fragments into a complete protein using a synthesis robot. The element boron plays the decisive role here. This should pave the way for new cancer therapies.

(CONNECT) Chemists at ETH Zurich have opened a door to the production of new cancer therapies that was previously firmly closed: according to a statement from the university, their new method now makes it possible for the first time to combine even poorly soluble protein fragments, which make up many proteins that are important for modern medicine and science, into new complete and functioning proteins.

With the methods known to date, this only works if these particles are dissolved in comparatively high concentrations. Poorly soluble proteins, on the other hand, clump together easily and therefore cannot be produced automatically in the laboratory.

For their new approach, the team led by Jeffrey Bode, Professor at the ETH Laboratory of Organic Chemistry, made use of the special properties of a chemical compound containing the element boron. The new linking method is 1000 times faster than conventional methods and therefore also works at 1000 times lower concentrations. This prevents the proteins from clumping together.

After many years of research, the team succeeded in protecting this boron compound from strong acids by chance - when a doctoral student tested a method that the team believed would not work. "This kind of fundamental research, in which we can venture into unknown scientific territory without any prospect of success, is only possible thanks to unrestricted funding from the Swiss National Science Foundation and ETH," Bode is quoted as saying.

Thanks to the ETH method, clumping-prone antibodies, protein drugs or medically important membrane proteins can now be produced using laboratory robots. In 2020, Bode himself co-founded the ETH spin-off Bright Peak Therapeutics, based in the Switzerland Innovation Park Basel Area, which uses the technologies developed in his research group to develop immunotherapies to fight cancer. An initial therapeutic agent is already undergoing clinical trials. The new boron-based method could help to further expand the start-up's product pipeline. ce/mm

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