From Peptides to Preeminence

Jane Aldrich, Ph.D., and Jay McLaughlin, Ph.D.
Jane Aldrich, Ph.D., and Jay McLaughlin, Ph.D.

For more than a decade, scientists Jane Aldrich and Jay McLaughlin relied upon phones and computers to bridge their worlds of opioid peptide research. Separated by nearly 1,400 miles, Aldrich, residing in the Midwest, and McLaughlin, living on the East Coast, shared a common pursuit of drug discovery.

“I joked that sometimes I would talk to Jay more on the phone than someone one floor up in my building,” Aldrich said.

In recent months, the phone conversations have been replaced by face-to-face meetings, as Aldrich and McLaughlin both joined the faculty at the University of Florida College of Pharmacy.

As the senior partner, Aldrich is among the country’s leading experts on peptide design and synthesis. Before joining UF, she spent 14 years as a professor of medicinal chemistry at the University of Kansas. Her impact on the field includes 100 journal articles, service on multiple editorial review boards for scientific journals, tenure as president of the American Peptide Society, chair of the Medicinal Chemistry Division of the American Chemical Society and a recent invitation to serve on the Center for Scientific Review’s Drug Discovery for the Nervous System Study Section.

Aldrich established her career making chemical compounds tested in cell-based assays to see how well they interacted with opioid receptors. The experiments were in vitro, or test-tube based. Her research team primarily made compounds that acted as antagonists — compounds that would block the activation of receptors by agonists and allow for further study of receptor functions.

As Aldrich developed this line of research, she discovered several compounds that were good antagonists, but her studies were limited to the test tube assays. She was unsure if the compounds would be stable enough for sufficient duration of activity in the body.

In 2005, Aldrich attended the International Narcotic Research Conference and struck up a conversation with McLaughlin, then a first-year assistant professor at Northeastern University with a background in neuroscience.

“We were sitting at this conference, and I said it would be interesting to test this peptide [arodyn] in animals, but it was going to be short acting because it is not really stable in the middle,” Aldrich said. “Jay said ‘that’s a good thing,’ and the conversation went from there.”

McLaughlin convinced Aldrich to send him the compound. Tests showed it blocked agonist activity at kappa opioid receptors in mice. At the same time, scientists discovered that the kappa opioid system was involved with stress responses — particularly the response to drugs of abuse. Aldrich and McLaughlin surmised that putting a kappa opioid in the body could block the activation of the receptors and potentially be used to treat drug abuse.

“All of a sudden this group of compounds had the potential for therapeutic applications,” Aldrich said.

The pair’s mutual curiosity in finding a short-acting antagonist spawned a decade of collaboration. Their first big research breakthrough came in 2007, when they looked at a peptide called zyklophin, which was previously synthesized in Aldrich’s lab.

“Zyklophin was an incredibly selective, highly effective, peptide kappa antagonist that as far as we could tell had very few side effects,” McLaughlin said. “That was one of our first real big hits, and when it was published in a very well respected journal [The Proceedings of the National Academy of Sciences], it grabbed a lot of people’s attention.”

Zyklophin proved to be challenging to synthesize and purify in large quantities. While Aldrich’s research group worked on scaling up the synthesis of zyklophin, Aldrich and McLaughlin began testing other compounds, looking for similar activity. In the process, their research garnered the attention of multiple funding sources. The collaborators secured two R01 NIH grants to study the peptides’ relationship to drug addiction and cocaine abuse.

With their research taking off, both scientists continued their respective careers a time zone apart. In 2009, McLaughlin accepted a position at Torrey Pines Institute for Molecular Studies in Port St. Lucie, Florida. The new role allowed him to apply his experience in behavioral science to study new compounds developed at Torrey Pines. Meanwhile, he continued to work with Aldrich on developing new compounds, writing papers and applying for grants.

“Jane had this interest in pharmacology and the background,” McLaughlin said. “What I was bringing was the behavioral experience. She had not had the opportunity to develop that, and I was bringing additional experience with pharmacology. That became a synergy that we could play off each other.

“She needed the additional partnership that I could provide, and I needed the additional compounds that she had. The two of us, with her as the senior partner, would start talking, and our conversations were two hours long every few days.”

A new twist in the partnership developed in 2014 when Aldrich was offered a position at the UF College of Pharmacy, and she suggested McLaughlin’s name as another potential hire.

The University of Florida’s Preeminence initiative was recruiting top scientists to join UF and help the university become an international leader in more than two dozen fields — including drug discovery and development. Within a matter of months, Aldrich and McLaughlin would become two of five Preeminence hires made by the College of Pharmacy.

“Working on the same campus is really giving our group members the chance to sit down and talk,” Aldrich said. “Chemists can talk to the biologists, and the biologists can learn more about the challenges of solubility and how it can limit the testing of compounds. I think it’s really going to strengthen the project feedback and our research.”

Recently, Aldrich and McLaughlin have been examining cyclic tetrapeptides as treatment options for drug addiction. The pair is also searching for pain killers that are safer, more potent and easier to use. The long-term goal is to some day advance a drug to human clinical trials. It is a goal made much more achievable thanks to the wealth of scientific and clinical resources available at the University of Florida.

No longer does the pair measure separation by miles, but rather by floors in a building. Aldrich’s office resides only three floors apart from McLaughlin’s. While face-to-face meetings are replacing the phone’s role in the relationship, the pursuit of drug discovery remains the ultimate goal.

“It’s going to be a lot of fun,” Aldrich said. “Science, when you get good results, can be exciting. I think there are some fantastic opportunities here at the College of Pharmacy to see what we can do with these compounds and see where they can go.”