New Enzyme Discovery Could Improve GLP-1 Drugs Like Ozempic and Wegovy
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Researchers at the University of Utah have identified an enzyme called PapB that can reshape therapeutic peptides into ring structures, a process known as macrocyclization. This discovery may be applied to GLP-1 medications, including semaglutide, potentially improving their performance. The technology, developed into a discovery platform, has already led to the founding of a new company, Sethera Therapeutics.
Facts First
- PapB enzyme performs macrocyclization, linking peptide ends into rings to create compact structures.
- The process may improve GLP-1 medications like semaglutide (Ozempic, Wegovy) by enhancing their performance in the body.
- PapB works without complex chemical techniques required by traditional methods, forming a sulfur-carbon bond called a thioether.
- Laboratory tests were successful on three different GLP-1-like peptides, converting all into ring-shaped versions.
- The discovery led to a new company, Sethera Therapeutics, co-founded by the researchers with NIH support.
What Happened
Researchers at the University of Utah identified an enzyme called PapB that can perform macrocyclization, a process that reshapes therapeutic peptides by linking their ends into tight rings. The study was published in ACS Bio & Med Chem Au. Laboratory experiments demonstrated that PapB creates ring structures even when peptides include nonstandard building blocks used in modern incretin drugs. The research team converted three different GLP-1-like peptides into ring-shaped versions using the enzyme.
Why this Matters to You
If you or someone you know relies on medications like Ozempic or Wegovy for diabetes or obesity treatment, this discovery could lead to future versions of these drugs that are more effective or longer-lasting. The macrocyclization process creates compact structures intended to improve how medicines perform in the body, potentially making them more resistant to being broken down by the body's natural recycling enzymes (proteases). This might mean more stable treatments that require less frequent dosing.
What's Next
The discovery has already been commercialized through the founding of Sethera Therapeutics last year by researchers Karsten Eastman and Vahe Bandarian, with support from the National Institutes of Health (NIH). The University of Utah's Technology Licensing Office named them the 2025 Founders of the Year for developing the PolyMacrocyclic Peptide (pMCP) Discovery Platform. The researchers may now work to apply the PapB enzyme technology specifically to develop improved versions of existing GLP-1 therapies.