Photo-activatable Reagents for Bioorthogonal Ligation Reactions

Light-induced bioorthogonal reactions offer spatiotemporal control over selective biomolecular labeling. This review covers the recent advances in the design of photo-activatable reagents for bioorthogonal conjugation reactions in living systems. These reagents are stable in the absence of light, but transformed into reactive species upon light illumination, which then undergo rapid ligation reactions. The light wavelength has been tuned from ultraviolet to near infrared to enable efficient photo-activation in reactions in deep tissues. The most prominent photo-activatable reagents are presented, including tetrazoles, tetrazines, 9,10-phenanthrenequinone, diarylsydnones, and others. A particular focus is on the strategies for improving reaction kinetics and biocompatibility accomplished through careful molecular engineering. The utilities of these photo-activatable reagents are illustrated through a broad range of biological applications, including in vivo protein labeling, positron emission tomography (PET) imaging, responsive hydrogels, and fluorescence microscopy. The further development and optimization of these biocompatible photo-activatable reagents should lead to new chemical biology strategies for studying biomolecular structure and function in living systems.