Optochemical Control of Protein Degradation
Peng Wu, Debasish Manna
Abstract
Abstract Optochemical approach has been successfully utilized to regulate cellular protein degradation with a high resolution of spatiotemporal control. In this highlight, we discuss two recent developments of combining reversible optochemical functionalities with the bifunctional proteolysis targeting chimeras, or PROTACs to achieve light‐controlled degradation of protein targets of interest. PHOTACs are azobeneze‐containing molecules that are inactive as trans forms and active as cis forms, switchable upon pulse‐irradiation with either an activating 390 nm light or a deactivating 525 nm light. In contrast, photoPROTACs are o ‐F 4 ‐azobenzene‐containing molecules that can be switched between active trans isomers and inactive cis isomers by a single irradiation event using 415 or 530 nm light. Combining these two optochemically controlled PROTAC systems has the potential to achieve orthogonal control on protein degradation.