And unlike most other molecular probes, this type identifies only active enzymes. "We went one step beyond just telling if the enzymes are there. We can answer the question, 'Are they active"' That's important because an accumulation of inactive enzymes doesn't necessarily indicate disease," Blum said.
Bogyo, Blum and colleagues designed the probe to bind to a subset of a family of proteases called cysteine cathepsins, which are more active in several types of cancer as well as other diseases. Now they are tinkering with the probe's configuration in an effort to create a variant that recognizes the enzymes involved in apoptosis, the process of cell death. This could ultimately allow researchers and doctors to visualize response to chemotherapy in tumors, Bogyo said.
And because other diseases besides cancer involve hyped-up proteases - such as Alzheimer's, arthritis, atherosclerosis and osteoporosis - the approach might be of use in diagnosing and treating them as well.
The work went surprisingly smoothly because of Blum's background in chemistry as well as biology. Using her chemistry skills, she created the probes. Then she switched to biology mode and tested them. When she discovered that an earlier version of the probe worked great in tissue culture but decomposed on contact with mouse blood, she was able to tweak the molecule's structure to survive inside a living animal.
In addition to the potential health-care applications, the approach provides a valuable research tool, the researchers said. "It allows you to see exactly where enzymes are active within living animals," said Bogyo.
The Stanford researchers' ultimate goal is to test it in humans, though they'll complete more testing in animals before requesting permission from the U.S. Food and Drug Administration to conduct a human trial. "Since there are currently no fluorescent imaging agents in use in humans, the approval process is likely to requir
|Contact: Rosanne Spector|
Stanford University Medical Center