Endogenous Proteins Modulation in Live Cells with Small Molecules and Light.

Protein modulation by light illumination enables the investigation of biological function in high spatiotemporal precision. Compared to genetic methods, the small molecule approach is uniquely suited for modulating endogenous proteins. Endogenous protein modulation in live cells with small molecules and light has recently advanced on three distinctive frontiers: i) the infrared-light-induced or localized decaging of small molecules by photolysis, ii) the visible-light-induced photocatalytic releasing of small molecules, and iii) the small-molecule-ligand-directed caging for photomodulation of proteins. Together, these methods provide powerful chemical biology tool kits for spatiotemporal modulation of endogenous proteins with potential therapeutic applications. This Concept article aims to inspire organic chemists and chemical biologists to delve into this burgeoning endogenous protein modulation field for new biological discoveries.