Endogenous Proteins Modulation in Live Cells with Small Molecules and Light

Abstract

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 releas-ing of small molecules, and iii) the small-molecule-liganddirected 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.

Construction of gel networksvia[2+2] photocycloaddition

“…Under the circumstances, the biocompatible and bioapplicable photocatalysis process was further investigated in vitro and in cellulo. [72][73][74][75][76][77][78][79][80][81][82] However, photocatalyzed [2+2] reactions were not developed in this field, nor the formation of gel network, probably due to the difficulties in the removal of the photocatalyst and some potential additives. As a result, the inductions of bio-compatible catalysis and leaving groups in the system would be crucial and green process of visible light photocatalyzed [2+2] will take a good effect in the construction of gel networks and the applications in biomedical science.…”

Photo‐Modulation of Gene‐Editing Enzymes CRISPR/Cas9 with Bifunctional Small‐Molecule Ligands†

“…[ 1‐4 ] Small molecules are valuable resources for addressing these challenges due to their easy delivery and fast disruption of endogenous proteins. [ 5‐7 ] The light‐triggered release of small molecules is promising for external modulation of protein functions in high spatiotemporal resolution. [ 8‐11 ] Typically, small‐ molecule inhibitors are caged with photoremovable protecting groups to restrict their inhibitory potency.…”