Your hands are mirror images of each other, and you still can’t wear a left-handed glove on the right one. Karl A. Scheidt, a chemist at Northwestern University, uses that picture to explain why a puzzle about rye pollen stayed open for nearly 30 years.
“It’s like your hands,” Scheidt said. “They are mirror images of each other, but you need a different glove for each.”
In the early 1990s, scientists found two unusual molecules in rye pollen that seemed to help animals fight tumors. Then the work stalled. Nobody could pin down the molecules’ exact three-dimensional structures, and without that, nobody could work out how they acted or how to copy or modify them.
Two models, one mirror-image difference
Standard methods, including advanced nuclear magnetic resonance spectroscopy, could not show how key parts of the molecules were arranged. For decades, researchers argued between two proposed structures. Both had the same atoms joined in the same way and the same overall shape. In one critical region, though, each model was the mirror image of the other. A difference that small can decide whether a molecule fits a biological target at all.
Scheidt’s team settled it by building the molecules themselves. This approach, called total synthesis, assembles a natural molecule step by step in the lab, and it proves a structure by construction instead of inference. The two compounds are now named secalosides A and B.
The job was hard. Both molecules have an extremely rare, highly strained 10-membered ring at the core, and that tightly compressed shape is notoriously difficult to make. The team first built a larger, more flexible ring, then set off a reaction that turned it into the strained ring in one step.
They made both proposed versions and compared each with samples extracted from rye pollen. Only one matched perfectly.
The results appeared in the Journal of the American Chemical Society, in a paper titled “Synthesis and structural confirmation of secalosides A and B.” The National Institute of General Medical Science, the Chemistry of Life Processes Institute Lambert Fellowship and the National Science Foundation supported the work.
What comes next
“In preliminary studies, other researchers found that rye pollen could help different animal models clear tumors through some unknown, non-toxic mechanism,” Scheidt said. “Now that we confirmed the structure of these molecules, we can find the active ingredient — or what part of the molecule is doing the work.”
He called it “an exciting starting point to make better versions of these molecules that could possibly inform approaches to cancer therapy.” Natural products, he added, “aren’t necessarily effective drugs on their own, but they are great leads.”
The history backs him up. Morphine comes from the opium poppy, Taxol was first isolated from the Pacific yew tree, and statins began with fungi. Camptothecin, from the Chinese happy tree, led to a class of topoisomerase inhibitors.
This result is not a treatment. Medical Daily stressed that most such leads never become approved drugs. The work is basic chemistry at the preclinical stage, and no clinical trials have been conducted or announced. Nothing here shows the molecules are safe or effective in people.
Rye pollen extract is already sold as a supplement that many people take for prostate health, but scientists have not developed it into a drug. Eating rye bread does not deliver the molecules in question, which were isolated from pollen in the lab.
“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.”
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. Anyone with questions about cancer care should consult their doctor.
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
