Chemistry professor Steven Castle was initially drawn to organic chemistry because of chemists’ ability to synthesize things that don’t exist in nature—which is exactly what his latest research focuses on.
Peptides tend to break down quickly in the body, limiting their use as drugs. Castle wants to synthesize a new form of peptides that will last longer.
“The research is based on trying to make peptides more stable,” Castle said. “You can synthesize peptides to do just about anything you want, but the reason why peptides have been underutilized as drugs is . . . their lifetime in the body is very short.”
As an example, Castle cited enfuvirtide, the only FDA-approved drug that blocks HIV viral membrane fusion, a peptide drug that has to be injected twice per day and in large doses.
“There are enzymes in the body that are designed to chop them up, so this severely limits the use of peptides as drugs,” Castle said.
Castle’s research was inspired by nature. In 2010, scientists found small amounts of yaku’amide A—a peptide and powerful anti-cancer agent—in deep-sea sponges.
“We realized the peptide contains dehydroamino acids and thought they might be important to its biological activity,” Castle said. “We thought, why not insert these bulky dehydroamino acids into other peptides and see what happens?”
The idea behind the project is not the first of its kind. However, previously scientists have been limited by their inability to synthesize peptides containing bulky dehydroamino acids.
“It took a team of students—a talented graduate student working with a couple of undergraduates—three years or so to come up with a way that we could synthesize these bulky dehydroamino acids,” Castle said.
Castle’s group discovered a way of inserting the bulky dehydroamino acids into peptides using a method known as solid-phase peptide synthesis.
The next step is testing whether peptide drugs that contain dehydroamino acids are more stable, while retaining the potency of the original drug.
“Hopefully in the future we’ll have some exciting results in this area,” Castle said.