Boskovic earns NSF grant to support new research for pharmaceutical drug discoveries

LAWRENCE — Zarko Boskovic, assistant professor of medicinal chemistry in the University of Kansas School of Pharmacy, has been awarded a $575,000 grant from the National Science Foundation. The grant will be used in the Boskovic Lab to shed light on the process of efficiently and selectively creating new molecules that hold potential for drug discovery. 

Boskovic and colleagues from KU Pharmacy and the Department of Chemistry will use photochemistry to see how molecules react to light, with the intent of creating diverse new and structurally intricate chemical compounds.

“We are bringing photochemistry into the 21st century,” Boskovic said. “The potential applications are in making new bioactive molecules for use in drug therapy. We are selectively infusing molecules with energy from light and controlling how the molecule reorganizes and rearranges itself in response to this excess energy.”

To explain this process of using photochemistry, Boskovic used an analogy of winding a spring to run a clock. 

“Unwound, or in its ground state, the spring just sits there doing nothing,” he said. “But when you wind it, you can take advantage of the work it does. That’s what we’re trying to do by exposing molecules to light — take advantage of the changes that the light creates.”

Scientists have been observing how light transforms molecules for more than a century. It’s a function of electrons within the molecule, and KU Pharmacy researchers have a long and strong history in photochemistry. The late KU professor Gary Grunewald and his mentor Howard Zimmerman at Wisconsin were pioneers in an early wave of photochemistry.

In fact, the NSF grant will help provide for the cataloging and reintroduction of thousands of compounds that have been in storage for years. 

“I like to call it a chemical heritage,” Boskovic said. “We have inherited tens of thousands of molecules from previous researchers at KU. We are organizing these collections, barcoding them and drawing the chemical structures. We have found some amazing pharmaceutical samples from as far back as the 1800s.”

Boskovic said his team will use some of the compounds for testing its methods and even share them with other researchers. 

“We were shocked when we looked at some of these 100-year-old samples with NMR spectroscopy. They looked better than some of the things we’re making today, in terms of purity and the sharpness of peaks. It’s remarkable and a valuable resource,” he said.

Researchers in the Boskovic Lab will use LED lights with different filters to control wavelengths of light. The molecules they study and create through this process can then be exposed to cells through cell painting. For example, a cancer cell could be exposed to these new compounds to see how they react. Observations and reactions will be recorded to help make conclusions about what the compounds might be doing in the cells. 

Other targets include exploring how new compounds will affect the central nervous system and how the compounds covalently react with proteins that cancer cells depend on to multiply.

Broader effects of the grant include helping both graduate and undergraduate students with computational literacy. 

“We are trying to connect the data to chemistry,” Boskovic said. “With AI permeating everything, we want students to understand the fundamentals and math behind it. What are the limitations? What are the possibilities? One of the undercurrents of this grant is to study how to more effectively use data.”

This is the first major grant Boskovic has secured, and he is excited for its potential to shed light on the benefits of photochemistry and the potential it holds for drug discovery. 

“It feels like a validation of my research program, because sometimes you wonder. It’s a significant form of feedback from your peers, so I’m thankful to the chemistry division of the NSF and to the American public,” Boskovic said. “It’s a huge investment on the public’s part, and I think it’s important that we have these opportunities to communicate to the public what we do.”