Two molecules from rye pollen have kept chemists guessing for nearly 30 years. Now a team at Northwestern University has settled it. Working in the laboratory, they built secalosides A and B from scratch and confirmed the exact three-dimensional structures, a result published in the Journal of the American Chemical Society.
The trail began almost three decades ago, when researchers found the two molecules in rye pollen and saw that they seemed to slow tumor growth in animal studies. Then the work stalled. Nobody could say precisely how the atoms were arranged in space.
Two models, one mirror image apart
Advanced nuclear magnetic resonance spectroscopy and other traditional techniques could not fully pin down how key parts of the molecules were laid out. For decades scientists argued over two candidate structures. Both had the same atoms joined in the same way, and both had the same overall shape. The only difference was that one critical region was a mirror image in each.
That small flip can change how a molecule interacts with biological targets, and whether it has any effect at all. Karl A. Scheidt, who led the study, reached for a familiar comparison. “It’s like your hands,” he said. “They are mirror images of each other, but you need a different glove for each. If you had two left-handed gloves, it wouldn’t work because your hands can’t be superimposed on top of one another.”
Building the answer
The team used total synthesis, in which researchers assemble a natural molecule step by step in the lab. It was hard going. Secalosides A and B have an extremely rare, highly strained 10 membered ring at their core, and a ring that tightly compressed is notoriously difficult to make.
The chemists got around it by starting with a larger, more flexible ring. A single chemical reaction then turned it into the smaller strained one.
They made both proposed versions and set each against samples extracted from rye pollen. Only one matched perfectly, which settled which structure was real.
What comes next
Scheidt is a professor of chemistry at Northwestern’s Weinberg College of Arts and Sciences and a professor of pharmacology, by courtesy, at the Feinberg School of Medicine. He described what the old animal work had shown. “In preliminary studies, other researchers found that rye pollen could help different animal models clear tumors through some unknown, non-toxic mechanism,” he said.
With the structure confirmed, he said, “we can find the active ingredient — or what part of the molecule is doing the work. This is an exciting starting point to make better versions of these molecules that could possibly inform approaches to cancer therapy.”
He pointed to a pattern in drug discovery. Morphine comes from the opium poppy, Taxol was first isolated from the Pacific yew tree, and statins originated from fungi. “Natural products aren’t necessarily effective drugs on their own, but they are great leads,” Scheidt said.
Rye pollen extract is already sold as a dietary supplement that many people take to support prostate health, but scientists have not developed it into a pharmaceutical treatment. Medical Daily noted that the work produces neither a cancer treatment nor a clinical candidate. No clinical trials have been announced, and the evidence for anti-tumor activity so far comes from early animal studies. Readers with health concerns should consult their doctor.
“We’ve demonstrated we can make the core of this natural product,” Scheidt said. “Now, we’re trying to find potential collaborators in immunology who could help us translate this to a possible clinical endpoint.”
The study, “Synthesis and structural confirmation of secalosides A and B,” was supported by the National Institute of General Medical Science, the Chemistry of Life Processes Institute Lambert Fellowship and the National Science Foundation.
Sources
- Scientists solve a 30-year rye pollen mystery that could transform cancer research
- Scientists Solved a 30-Year-Old Mystery About Rye Pollen's Anti-Tumor Properties
- Scientists solve a 30-year rye pollen mystery that could transform cancer research
