Amine-Reactive Activated Esters of meso-CarboxyBODIPY: Fluorogenic Assays and Labeling of Amines, Amino Acids, and Proteins

• Published in: Journal of the American Chemical Society 2020-05, Vol.142 (20), p.9231-9239
• Main Authors: Jeon, Sungjin, Kim, Tae-Il, Jin, Hanyong, Lee, Uisung, Bae, Jeehyeon, Bouffard, Jean, Kim, Youngmi
• Format: Article
• Language: English
• Subjects: Amines - analysis; Amino Acids; Animals; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Cell Line, Tumor; Esters - chemical synthesis; Esters - chemistry; Fishes; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Humans; Molecular Structure; Optical Imaging; Proteins - analysis
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.9b13982

Fluorescence-based amine-reactive dyes are highly valuable for the sensing of amines and the labeling of biomolecules. Although it would be highly desirable, large changes in emission spectra and intensity seldom accompany the conjugation of known amine-reactive dyes to their target molecules. On the contrary, amide bond formation between amines and the pentafluorophenyl (2-PFP) and succinimidyl (2-NHS) esters of meso-carboxyBODIPY results in significant changes in emission maxima (Δλ: 70–100 nm) and intensity (up to 3000-fold), enabling the fast (down to 5 min) and selective fluorogenic detection and labeling of amines, amino acids, and proteins. This approach further benefits from the demonstrated versatility and high reliability of activated ester chemistry, and background hydrolysis is negligible. The large “turn-on” response is a testament of the extreme sensitivity of meso-carboxyBODIPYs to the minimal changes in electronic properties that distinguish esters from amides. Applications to the detection of food spoilage, staining of proteins on electrophoretic gels or in living cells, and the expedited synthesis of organelle-specific fluorescence microscope imaging agents are further demonstrated.