Bandarian, professor of chemistry and associate dean in the College of Science, researches enzymes whose function is unknown but give the cell some sort of advantage. “We basically pick a class of enzymes or a class of molecules and then look at every level from how they're made, what the actual enzyme does, all the way down to the atomic level,” Bandarian says. “We are a lot more focused on discovering new and cool chemistry and enzymes.”

When then-graduate student Karsten Eastman joined Bandarian’s lab, Eastman hopped on one of the available projects, and through some serendipity Eastman and Bandarian realized the enzyme they were studying had the potential to change peptide-based therapeutics.

Typically, enzymes have one job to perform, but this particular enzyme was doing a lot more than normal. “We realized that we might be able to apply this to start making better versions of therapeutics already on the market,” Eastman says. “Once we had this aha moment of, ‘Hey, look, we can actually use this molecular machine to do work on a lot of different things,’ that set everything in motion.”

What they discovered was a way to introduce a better alternative to a disulfide bond. Many peptides and proteins in a human body use these disulfides—or a connection between two sulfur atoms—in their structure, essentially dictating how rigid the structure is. The problem is these disulfides can cause compounds to have a short half-life because the structure is easy to break apart, allowing the body to digest it quickly.

“Now that's great when you're trying to regulate things normally within the body. However, from a therapeutic standpoint, that's a big problem,” Eastman says.

Eastman and Bandarian were able to engineer a process by which an enzyme can install a thioether—sulfur to carbon—bond within a peptide, rather than a disulfide. “It's a much stronger bond. And what that allows us to access is a therapeutic that essentially doesn't have that downside of the short half-life,” Eastman says.

Read the full story on the U's Technology Licensing website.
Watch a video featuring Karsten Eastman on the research at the Utah Life Sciences Summit below.