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 first the use of a coumarin modified triazabutadiene that can deliver aryl diazonium ions to fluorescently label proteins via tyrosine selective modification. The labeling can be triggered by low pH induced liberation of the diazonium species, making the fluorophore specifically useful in labeling biochemical surroundings such as those found within the late endosome. Additionally, we show that a variety of coumarin triazabutadienes may also be prone to releasing their diazonium cargo via irradiation with UV light.

Ullmann‐Goldberg and Buchwald‐Hartwig C−N Cross Couplings: Synthetic Methods to Pharmaceutically Potential N‐Heterocycles

“…Five-membered N-heterocycles can also be used for clinical research goals such as protein labeling. [25,26] Sevenmembered N-heterocycles, especially benzodiazepine derivatives, are important structural scaffolds in many drugs. [7] From the long list of drugs containing these compounds, Olanzapine can be mentioned.…”

“…It is an angiotensin II (AII) receptor antagonist used for patients with hypertension [21–24] (Figure 1 – Entry F). Five‐membered N‐heterocycles can also be used for clinical research goals such as protein labeling [25,26] . Seven‐membered N‐heterocycles, especially benzodiazepine derivatives, are important structural scaffolds in many drugs [7] .…”

Crystal structure and spectroscopic properties of (E)-1,3-dimethyl-2-[3-(4-nitrophenyl)triaz-2-enylidene]-2,3-dihydro-1H-imidazole

“…They have been used in medicinal, combinatorial chemistry, in natural synthesis and as organometallic ligands (Kimball et al, 2002). In chemical biology, masked diazonium ions (triazabutadienes) have found use on protein surfaces for identifying host proteins that interact ISSN 2056-9890 during early stages of viral entities (Jensen et al, 2016;Shadmehr et al, 2018). In addition, triazabutadienes have shown tunable reactivity under specific conditions.…”

Coumarins as Fluorescent Labels of Biomolecules

“…Does not react with methionine, histidine, or tyrosine [68,80,109] hydroxyl groups do not allow highly specific labelling reactions due to the existence of several hydroxyl groups in biomolecules (serine, threonine, and tyrosine) [113]. One of the well-known labelling methods is the reaction with diazonium salts resulting in the formation of azo compounds, as 4-trifluoromethylcoumarin-7-diazonium chloride [114]. Although these aryl diazonium ions are promising for the desired application, their storage and delivery are challenging, and they often require in situ generation.…”