Azobenzene Photoswitches in Proteolysis Targeting Chimeras: Photochemical Control Strategies and Therapeutic Benefits

Abstract

The photoswitchable-PROTACs have photoswitches that work as an actual ON/OFF switch for any particular bioactivity. In reported studies, the ON/OFF activity correlates with the photostationary state and quantum yield of a specific isomer under a definite wavelength of light, providing a spatiotemporal control over protein degradation (an example of photochemistry-based precision medicine). The studies reported the role of azobenzenes as photoswitches (ortho-tetramethoxybenzenes, ortho-tetraflurobenzenes as push-pull and push-push) to develop light-controlled PROTACs. This paper discussed the photophysical properties of photoswitchable-PROTACs (such as photoisomerization, quantum yield, and thermal relaxation states) and correlated their photochemical-based structural bioactivity relationships. The proteins studied under photoswitchable-PROTACs are kinase proteins: BCR-ABL fusion protein, ABL; Bromodomain proteins: BRD2, 3, 4; Immunophilins: FKBP12.