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New Tool to Watch Real-Time Chemical Activity in Cells

Attempts to identify potential drugs that interfere with the action of one particular enzyme linked to heart disease and similar health problems led scientists// at Johns Hopkins to create a new tool and new experimental approach that allow them to see multiple, real-time chemical reactions in living cells. Their report on the work is published July 21 in the journal ACS Chemical Biology.

Most current drug development operations test chemicals on enzymes isolated from their normal environs and then take further steps to see if the chemical can get into the cell to do its work, and figure out how poisonous the chemical is to a cell.

“Living cells are critical to our work because they show us how and what is actually happening in a normal context and time span when a chemical is added,” says Jin Zhang, Ph.D., an assistant professor of pharmacology and molecular sciences in Hopkins’ Institute for Basic Biomedical Sciences.

Testing chemicals on enzymes in living cells provides the opportunity to find potential drugs that work in new ways. For example, using living cells allows researchers to “see” where in the cell chemicals do their work. Scientists could then design new drugs to go to specific places within cells to work more efficiently. Also, streamlining the one-at-a-time approach offers the chance to study - and rule out or in - many potentially useful chemicals at once.

What Zhang’s team developed is a biosensor and simple testing procedure that tells if a particular enzyme - called PKA - that acts like a “switch” is “on” or “off” in a living cell. The group has been focused on trying to understand and interfere with this enzyme switch, because if the enzyme is turned on at the wrong time or at the wrong place within cells, it can lead to cells misbehaving, which ultimately can lead to heart disease.

In the course of their work, the team built a protein biosensor that indicates if an enzyme located nearb
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