Ontwikkeling van foto-activeerbare protease inhibitoren en activity-based probes, en hun toepassing in de studie van dynamische proteolytische processen

Proteases are involved in many highly regulated biological processes, such as apoptosis, cell-cell communication and blood coagulation. Inhibitors and activity-based probes (ABPs) have been successfully utilized as chemical tools to study these enzymes. However, when studying fast and dynamic processes, local and temporal acivation of these reagents is desirable. Such reagents can first of all be used for basic study of these processes, but also be utilized as therapeutics that can benefit from local activation (i.e. in a tumor tissue), leading to lower side effects in the rest of the body. In this project, we will design, synthesize and test inhibitors and ABPs for proteases that can be activated by light. We will initially focus on the usage of photo-labile protecting groups that mask elements of the small molecules that are critical for protease recognition, and we will test these in models of apoptosis. At a later stage, we will try to broaden this strategy towards other protease families.