Ring Leader

A newly discovered enzyme could help create better versions of popular weight-loss and diabetes drugs like Ozempic and Wegovy, according to U chemistry researchers.

The enzyme, called PapB, ties drug molecules into tight rings—like tying a string of beads into a bracelet. When drugs are shaped into rings, they last longer in the body and work more effectively.

These medications are built from peptides, which are chains of amino acids that act like small proteins. However, the human body breaks down peptides quickly, sometimes within minutes.

“What we show in the study is an enzymatic method—using a tiny molecular machine to modify or hyper-modify peptides in extremely controlled ways,” says Karsten Eastman PhD’23, a U research associate in chemistry.

Right now, turning peptides into rings is expensive and complicated. PapB offers a simpler way to do it.

The team tested PapB on three different peptide-based drugs similar to Ozempic. In each case, the enzyme successfully tied the molecule into a ring.

The result? Drugs that stick around longer. By protecting peptides from the body’s natural recycling system, PapB could extend a drug’s effects from minutes to hours or more—making medications more effective and potentially requiring fewer doses.