Bioorthogonal chemistry has been wildly used in many fields, including cell imaging in chemical biology, protein targeting in clinical research, and drug-release in pharmacology. Typically, the bioorthogonal reagents have been optimized for stability in physiological conditions and rapid reaction rates. However, few reports have explored developing controllable bioorthogonal reagents, which can be activated by an external stimulus (e.g., light, enzyme, or metabolites) to regulate the bioorthogonal reactivity in a spatiotemporal manner. Here, we report our current work on discovering the temporally controlled reaction between caged cyclopropene analogs and inverse electron demand Diels–Alder (iEDDA) substrates. This work has concentrated on three directions: (1) Expanding the utilities of different types of caging groups on cyclopropene to initiate the bioorthogonal ligation with different stimuli. (2) Optimizing the reactivity of the cyclopropene scaffold by either modifying the functional group or expanding/narrowing the fused ring on cyclopropene derivatives. (3) Investigating various iEDDA substrates as the bioorthogonal reaction partner with the cyclopropene and exploring each pair’s utility for protein labeling and cell imaging.

Bioorthogonal reagents discovering and optimization for bioimaging

ACS Spring Meeting 2021

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