Quinone methide is a highly reactive species that can be generated from stable masked precursors. Due to their extraordinary electrophilic reactivity, quinone methide has been widely used in chemical biology as a trapping moiety. It was originally employed in the design of covalent inhibitors, then this concept has been extended to other functional molecules such as activity-based probes, and self-immobilizing fluorogenic substrates. Mostly, the quinone methide precursor adopts an orthro-difluoromethyl moiety on a phenol caged by a moiety that can be cleaved by a specific stimulus, followed by an 1,4-elimination to generate the quinone methide. Mechanisms affecting the activation reaction and the labeling step can affect the labeling efficiency. Herein, we synthesized a series of <i>beta</i>-galactosidase substrates with various substituents on the phenol moiety to probe the substituent effect. Fluorescent western blot experiment and flow cytometry were performed to compare the labeling efficiency of various substituents. This result can be used as a guideline for the design of activity-based probes and self-immobilizing fluorogenic substrates with high labeling efficiency.

Tuning the efficiency of quinone methide chemistry via electronic effects

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.