Wooster Scientists Discover Unique Cross-Linking Characteristic of Molecule

Finding by James West and Chelsea Stamm could have significant impact on future research

WOOSTER, Ohio — What began as a fairly routine study of unsaturated carbonyl compounds commonly used in biomedical research ended with several significant but unexpected outcomes for James West, assistant professor of biochemistry and molecular biology at The College of Wooster, and his fellow researcher Chelsea Stamm, a senior biochemistry and molecular biology major at Wooster, along with Philip J. Kingsley, an assistant in biochemistry at Vanderbilt University’s School of Medicine.

The three scientists looked at a number of structurally similar molecules known to kill skin cells and hypothesized that their toxicity would be comparable. However, they quickly learned that one of the molecules, diethyl acetylenedicarboxylate (a.k.a., DAD), was considerably more potent, so they began to search for a chemical explanation.

“What we found was that the molecule (DAD) can react with one protein and then cross link it with another protein, like molecular glue,” explained West, who has been studying protein damage by reactive molecules for the past decade. “None of the other molecules can cross link proteins, which is one way to explain why it is so toxic.”

The discovery is noteworthy because it provides a biochemical tool according to West, who recognized Stamm as a key player in the discovery of DAD as a protein cross-linker. “We can use it to find binding partners of proteins,” he said. “If we know that a protein in the cell has been modified by DAD, we can begin to ask questions about the other proteins to which it binds and becomes cross-linked. Like people, you can tell a lot about proteins by the company they keep. DAD can help us identify these interactions.” The jury is out on the long-term impact of these findings, but West believes it will be useful to biologists and chemists. “We've never seen anything quite like this before, in terms of how potent this molecule is,” he said. “It just stunned us.”

The research, which will be published this month in the American Chemical Society’s journal, Chemical Research in Toxicology, was supported by start-up funds, faculty-development funds, and William H. Wilson Research Funds from The College of Wooster as well as a grant from the Howard Hughes Medical Institute Undergraduate Science Education Program.