New Enzyme Could Make Ozempic Work Longer: The PapB GLP-1 Breakthrough Explained

# New Enzyme Could Make Ozempic Work Longer: The PapB GLP-1 Breakthrough Explained

> **Quick answer:** University of Utah scientists discovered an enzyme called PapB that converts GLP-1 drug peptides — the same class as semaglutide in Ozempic and Wegovy — into compact ring structures. These rings resist the body's protein-digesting enzymes, potentially making weight loss drugs last longer, work more reliably, and require fewer injections. Researchers have already spun off a company, Sethera Therapeutics, to bring this technology to clinical development.

A team of chemists at the University of Utah has found an enzyme that could make drugs like Ozempic significantly more durable in the human body — a discovery that may reshape how the next generation of GLP-1 weight loss medications are designed and manufactured. The research, published in *ACS Bio & Med Chem Au*, introduces a molecular tool that could extend how long semaglutide-like drugs stay active, potentially reducing the need for weekly injections and improving outcomes for millions of patients.

## What Is PapB and What Does It Actually Do?

The enzyme is called PapB, and it belongs to a class of biological machines known as radical SAM (S-adenosyl-L-methionine) enzymes. These are nature's precision cutters — enzymes that use a specific chemical reaction powered by a sulfur-containing molecule to modify other molecules in highly controlled ways.

What PapB does to GLP-1 peptides is called **macrocyclization**: it takes the open-chain strand of amino acids that makes up a drug like semaglutide and links both ends together with a sulfur-carbon bond called a thioether. The result is a ring-shaped peptide — chemically closed, compact, and structurally more resistant to degradation.