Making Better Medicine
Cottrell Scholar Grace Stokes is exploring the power of peptoids in helping develop longer-lasting drugs.
On a fundamental level, the human body processes all peptide-based drugs the same way. The drug is absorbed into the body and distributed into the bloodstream, then the peptides are broken down by enzymes in the liver and the drug leaves the system.
For something like ibuprofen, that process takes about six hours, which works great for a mild headache. But for other kinds of drugs—like cancer medication—that might not be ideal. What if doctors want the medication to work longer?
Grace Stokes, assistant professor in chemistry and biochemistry, is hoping to help drug companies do that. Her research on peptoids, which recently earned a Cottrell research grant worth $100,000, aims to help drug companies slow the breaking down of medication in the body by using synthetic peptoids instead of peptides.
“Peptides, because they’re natural, the enzymes in your body know how to break those down,” Stokes says. “Peptoids are synthetic. There’s nothing natural. But they’re more stable in that they don’t get degraded by enzymes in your body the same way.”
Specifically, Stokes wants to track the way peptoids interact with different kinds of cell membranes. The longer enzymes take to break down the peptoids, the longer a drug could work. With the results, scientists would be able to develop mathematical models that would help with the creation of new drugs.
“If we were able to make a library of different drugs and look at how those interact with some models of human cells, we might get some more predictive ability,” Stokes says. “So big picture, we would have some information that could help inform people as they design new drugs on what kind of characteristics they’re looking for.”
Jacenda Rangel ’18, one of the students working with Stokes on this research, thinks this research could have a big impact on how doctors are able to treat people.
“I like the potential therapeutic aspects of it,” Rangel says. “Looking at peptides, and how they can interact with the membrane could be extended to a much more complex and dynamic real system.”
Stokes is using synthetic cells in her research, which means these mathematical models won’t offer a one-to-one narrative of how a peptoid interacts with a specific cell in a living human body. That’s valuable research—and is being done elsewhere—but Stokes is coming at it from another angle, which is impactful in a different way.
By using synthetic cells, Stokes can control a whole host of factors like how rigid the structure of the cell membrane is or the components of the functional groups located on the backbone of the peptoid.
That means the data doesn’t just speak to interaction with whole cells, but it breaks it down further. If this research were like baking, using real human cells would be buying a box of cookies at a store and running tests. By using synthetic cells, Stokes makes her own cookies and controls each of the ingredients. That way, she can potentially determine the impact of an extra tablespoon of sugar or flour—or, a certain arrangement of functional groups in a peptoid.
And the $100,000 from the Cottrell Grant will help make this research more efficient. In addition to providing funds for more student workers, it also allows for upgrades to equipment, which would make a process with multiple changeable components not take quite as long.
“Instead of just testing one variable at a time,” Stokes says, “we can test maybe 48 variables at a time.”
Stokes and her student workers have already published several papers about their research in publications like Langmuir and The Journal of Physical Chemistry, with a few more on the way. Rangel is working on a paper right now that she would be the lead author on. She hopes to finish before she graduates this year.
Stokes says giving students like Rangel experience with research is one of the reasons she came to Santa Clara to teach. By attending conferences and writing papers, students like Rangel learn they’re part of the scientific community and can be a part of meaningful progress in their field.
“The idea is not necessarily the output of our lab, it’s the training of our students who can then go to discover new drugs and understand different types of interactions in the future. So they can take it wherever they want,” Stokes says. “I love doing the research but really, it’s their training that is going to have the longer-term impact.”
Mar 17, 2018
Grace Stokes and Jacenda Rangel ’18 use green lasers to study how peptoids interact with cell membranes.