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One of the longstanding challenges in chemical biology has been finding ways to directly observe biological processes at work inside living cells without disturbing the action. In order to unlock new therapies and better understand disease processes and other biological phenomena, scientists have used different methods of tracking molecular interactions inside cells in real time, a practice known as biomolecular labeling.

But current methods have limitations, creating unwanted chemical reactions or harming cells in the process. Now, a team of Northeastern University researchers think they've found a way to make biomolecular labeling safe for live cells by harnessing the power of "click chemistry," a process by which scientists generate chemical reactions to create new chemical formulas.

Sara Rouhanifard, a Northeastern assistant professor specializing in click chemistry and RNA imaging, says she and a team of research scientists created a breakthrough reagent they call "InCu-Click," a novel tool they say will help aid in drug discovery, diagnostics and biological research.

That tool is what's called a , a chemical agent that binds to copper, thereby mitigating its toxic effects on human cells. Rouhanifard says the reagent, which she says will better enable biomolecular labeling, was the result of "an accidental finding based on a failed experiment."

"It was kind of an accident," she says.

Rouhanifard and her colleagues published the in Nature Communications.

Researchers in Rouhanifard's lab have been focused on one particular chemical reaction called the copper-catalyzed azide-alkyne cycloaddition (CuAAC), an early example of click chemistry that's come to have widespread application as a way of creating new complex molecules out of chemical building blocks, such as proteins, amino acids and peptides.

That Lego-like joining of molecules, called covalent conjugation, has applications in a wide variety of fields, from biomedical research to nanotechnology.

But the CuAAC reaction, considered the bedrock of click chemistry, has never been viable for live cell research, a promising market projected to exceed worldwide.

"Nobody has ever been able to track biomolecules using the CuAAC reaction inside of live cells, and the reason is because copper is toxic to cells," Rouhanifard says. "You can't just put copper into cells because it will kill them."

That's where the copper-chelating ligand comes in. The reagent neutralizes the copper to such a degree as to prove safe in live cells, while still enabling the reaction to take place efficiently.

The tool also brings the necessary precision to the task: it is highly selective, meaning scientists can better isolate and study different functional groups—classes of molecules inside cells that serve a shared purpose—without compromising or harming others.

"All of these things are important," Rouhanifard says. "Live cell labeling is all about protecting the cell and doing things quickly."

Imaging techniques developed over the last century, such as , have made it possible for scientists to better identify and differentiate molecular structures of cells in microscopy.

"Usually, we're looking at cells in a snapshot," Rouhanifard says. "We're looking at something that is fixed. But molecules are dynamic. They're moving around in response to things going on in their environment, and we've been trying to find ways of visualizing that environment more readily."

Rouhanifard and her team hope to make InCu-Click available to biotech and pharmaceutical researchers and companies for widespread use. They are now focused on fine-tuning the copper-chelating ligand to get it ready for commercialization.

Rouhanifard says she hopes the advancement can translate to her ongoing research in gene expression and disease development.

"What we'd really like to achieve with this new reaction is to be able to track single molecules of RNA inside of live cells without having to genetically engineer them," Rouhanifard says.

"I want to be able to get a patient sample, for example, and be able to see how the RNA is moving around that cell, and how can I control it so that it doesn't do that in disease. The goal, essentially, is to cure human disease."

This story is republished courtesy of Northeastern Global News .