UC Irvine

Bioorthogonal chemistries enable the selective visualization and identification of biomolecules in complex cellular environments. Significant advances in the speed and selectivity of these reactions have been reported over the past few years. Despite these successes, challenges remain in applying bioorthogonal chemistries to studies of complex biological functions. Many bioorthogonal reagents cross-react with one another, limiting their utility for visualizing multi-component processes. Additionally, many bioorthogonal reagents are not small or stable enough to label native biomolecules in living systems. To address these issues, I have developed new classes of functionalized cyclopropenes for bioorthogonal labeling experiments. These small motifs are stable in cells and other environments, yet robustly reactive with tetrazines and various 1,3-dipoles. Cyclopropenes can also be readily tuned to elicit desired covalent reactivity, facilitating the development of “mutually orthogonal” bioorthogonal transformations. I utilized these bioorthogonal cyclopropene chemistries to target glycans and proteins, as well as to tag cells with imaging agents for in vivo cell tracking.