Coumarin Triazabutadienes for Fluorescent Labeling of Proteins

Abstract

The use of small-molecule fluorophores to label proteins with minimal perturbation in response to an external stimulus is a powerful tool to probe chemical and biochemical environments. Herein, we describe the use of a coumarin-modified triazabutadiene that can deliver aryl diazonium ions to fluorescently label proteins by tyrosine-selective modification. The labeling can be triggered by low-pH-induced liberation of the diazonium species, thus making the fluorophore especially useful in labeling biochemical surroundings such as those found within the late endosome. Additionally, we show that a variety of coumarin triazabutadienes might also be prone to releasing their diazonium cargo after irradiation with UV light.

Keywords: electrophilic substitution; fluorescent probes; protecting groups; protein modifications; substituent effects.