“For five years, I have been trying to explain my doctoral research to my wife, but I don’t think I’ve succeeded,” laughs Toms Upmanis, who successfully defended his doctoral dissertation at the University of Latvia in November last year.
His research, titled “Studies on the Mechanisms of Chiral Recognition for Chromatographic Separation of Short Peptides on Crown Ether Stationary Phases”, has gained significant recognition in the scientific community. Experts highlight that his work in analytical chemistry paves the way for future drug development, aiming to reduce side effects and create more targeted treatments for specific health conditions.
Small vs Large Molecules
Most medications we use today—such as painkillers (Ibuprofen, Aspirin), antibiotics (Penicillin, Tetracycline), or diabetes drugs (Metformin)—are small-molecule compounds. Their relatively simple chemical structures facilitate drug development, but at the same time, they contribute to side effects. Small molecules do not always reach their intended target effectively or act solely on a specific receptor in the body. Consequently, the pharmaceutical industry is actively exploring a shift from small-molecule drugs to larger, more selective compounds with fewer potential risks.
Peptides—chains of amino acids arranged in a specific sequence—are particularly well-suited for this purpose.
Why Large Molecules Represent the Future of Drug Development
The biological function and physical properties of peptides depend heavily on their three-dimensional (3D) structure. Naturally occurring amino acids are chiral (asymmetrical) and exist in either D- or L-forms. Peptides formed from these amino acids create complex chiral molecules that can exist as various stereoisomers (structurally identical molecules arranged differently in 3D space).
On the one hand, combining different amino acid configurations in peptide structures enables scientists to design highly selective drugs that act only on specific sites in the body. These large-molecule compounds, with multiple chiral centres, are thus significantly more precise or “intelligent.”
However, there’s a big challenge: as peptides get longer, the number of possible 3D variations increases exponentially, making it incredibly difficult to separate and analyze them. That’s where Toms’ research comes in.
Breaking Down Complex Peptides – One Step at a Time
“Science is like passing a relay baton to the next runner,” says Toms. “By studying literature and research, you find the point where someone else stopped. If you see value in continuing and have an idea on how to proceed, that stopping point becomes the starting line of your own work.”
Toms set out to create a systematic method for separating and identifying peptide variations. His approach combined multiple chemistry techniques, including:
Chiral Liquid Chromatography – a method to separate peptide variations based on how they interact with specialized materials.
Organic Synthesis – the ability to create peptide molecules in the lab.
Spectroscopy & Mass Spectrometry – tools that help visualize molecular structures and their interactions.
His experiment focused on a previously overlooked pain-relief peptide, YRFK-NH₂, which can exist in 16 different 3D forms. Toms was the first to synthesize all 16 variations and successfully separate them, setting a new milestone in peptide research.
Separate. Measure. Understand. Repeat.
To carry out this separation, Toms used liquid chromatography. In this method, a dissolved mixture of the target compounds is introduced into a chromatographic column—a 15 cm-long metal tube packed with a solid sorbent, typically silica gel. The sorbent is chemically modified with a specific compound—in this case, a crown ether. The structure of the sorbent is designed to interact differently with the peptide’s various stereoisomers, selectively “recognising” them. Depending on the strength of these interactions, some stereoisomers exit the column faster than others. While the general mechanisms of chiral separation in chromatography are well known, their molecular-level details remain largely unexplored.
To delve deeper, Toms turned to techniques more commonly used in biological research, such as nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, to observe and understand why different stereoisomers interact with the sorbent in distinct ways.
A Method That Opens Doors to Next-Generation Medicine
As a result, Toms developed a methodology for the chiral separation of large molecules (peptides) and established a knowledge base on how and why different spatial structures of large molecules undergo chromatographic separation.
His peers worldwide acknowledge that his contributions represent a significant breakthrough in analytical chemistry and pharmaceutical science, laying the groundwork for next-generation drug development.
His research has been published in several prestigious international scientific journals and widely cited. Toms expresses a strong desire to continue his work in the field of chiral recognition and strengthen research in this area within Latvia.
“We are already capable of producing world-class science. Over the years, we have built connections within the small global community of scientists dedicated to chiral recognition research. We now have the opportunity to communicate and collaborate continuously. I firmly believe that we still have plenty of valuable discoveries to share with the world,” says Toms.
Balancing Science and Everyday Life
Toms Upmanis comes from a family with three generations of experience in chemistry and pharmaceuticals. Although he initially considered studying medicine, circumstances led him down the “family’s traditional path.” Nevertheless, through his research and scientific work, he remains closely connected to both pharmacy and medicine.
He acknowledges that unlike more conventional professions—where conversations, complaints, or even jokes about work come naturally—chiral recognition mechanisms in liquid chromatography are not exactly dinner-table discussion material.
“But I don’t mind at all,” he says with a cheerful smile. “No matter how complex the questions I tackle, I’ve learned to leave work at work.”
Leaving the institute, Toms crosses the bridges over the Daugava River towards Pārdaugava. On his way home, he fully immerses himself in everyday life—the traffic jams, the breathtaking sunsets over the river, the shopping list for the grocery store, his home, and his loved ones. Meanwhile, back in the lab, science patiently awaits the next morning and the next breakthrough.
What’s Next?
Thanks to scientists like Toms, the future of medicine is shifting towards safer, smarter, and more targeted treatments. His research is a vital step in making large-molecule drugs a reality—helping patients get more precise therapies with fewer side effects.
And for Toms? His journey is just beginning. The next big discovery could be just around the corner.