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Scientists know a lot about apoptosis, from its molecular control to pathways that stop the cell death process in its tracks, but being able to control when and where it occurs would help researchers glean more details about its role in development. To that end, chemical biologist Steven Verhelst of KU Leuven in Belgium and his PhD student Suravi Chakrabarty decided to use a technique called photocaging to make an inhibitor of caspases, enzymes involved in apoptosis, that can be controlled by light.
For a small molecule to effectively inhibit a caspase, it needs a negative charge in just the right spot to fit into a positively charged pocket of the enzyme. Verhelst and Chakrabarty decided to develop a molecule that had a photocage, a chemical group that sat on top of that negative charge and prevented the inhibitor from binding and stopping the caspases from carrying out apoptosis. “If we could block that negative charge, we would virtually know well, say, 99 percent sure that it