Optochemical Control of Protein Degradation

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-F₄ -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.