Protein Switches: Safer Medicines – UW Medicine
- A new technique allows researchers to control the duration of protein-molecule binding, possibly leading to safer and more effective medications.
- Proteins frequently bind to other molecules to initiate biological processes like immune responses and metabolism.
- David Baker, professor of biochemistry at the University of Washington School of Medicine and a Howard Hughes Medical Institute investigator, explained, "We've added a second lever by designing...
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Scientists Develop ‘Switchable’ Proteins for More Precise Drug Control
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A new technique allows researchers to control the duration of protein-molecule binding, possibly leading to safer and more effective medications. The findings, published September 24, 2024, in Nature, offer a second mechanism for regulating drug activity beyond dosage.
The Challenge of Protein Stickiness in Drug Advancement
Proteins frequently bind to other molecules to initiate biological processes like immune responses and metabolism. However,this inherent “stickiness” can pose challenges in drug development. Once a protein drug, such as an antibody, begins to activate the immune system, it can be challenging to quickly stop its activity if adverse side effects arise according to the study.
Traditionally,drug control relies on adjusting the dosage. David Baker, professor of biochemistry at the University of Washington School of Medicine and a Howard Hughes Medical Institute investigator, explained, “We’ve added a second lever by designing molecules that can be switched off rapidly, even after they’ve taken full effect.”
How the ‘Switchable’ Proteins Work
The research team, based at the Baker Lab,employed computational methods to design custom proteins capable of binding to specific target molecules. Crucially, they introduced a separate molecule, termed an “effector,” which, when added, induces a strained configuration within the protein complex, causing it to dissociate.
This approach differs from previous methods that focused on altering the strength of the initial protein-molecule binding. Rather, it directly controls the duration of the interaction. In experiments detailed in the Nature publication, interactions that typically lasted 20 minutes were disrupted in as little as 10 seconds.
Implications for Safer and More Effective Medicines
The ability to rapidly deactivate protein drugs has important implications for patient safety. For instance, in immunotherapies, where the goal is to stimulate the immune system to fight cancer, an overactive immune response can lead to dangerous autoimmune reactions. This new technology could provide a crucial safety net, allowing clinicians to quickly halt the drug’s activity if such complications arise.
beyond immunotherapy, the “switchable” protein technology could be applied to a wide range of therapeutic areas, including:
- Enzyme inhibitors: Precisely controlling the duration of enzyme inhibition could minimize off-target effects.
- Hormone therapies: Rapidly adjusting hormone levels could improve treatment outcomes and reduce side effects.
- Neurological disorders: Fine-tuning neurotransmitter signaling could offer new therapeutic avenues.
Timeline of Key Developments
| Date | Event |
|---|---|
| September 24, 2024 | Research published in Nature detailing the development of ‘switchable’ proteins. |
| Ongoing | Further research and development to translate the technology into clinical applications. |