Rational Design of Fluorogenic and Spontaneously Blinking Labels for Super-Resolution Imaging.
ACS Cent Sci
Rhodamine dyes exist in equilibrium between a fluorescent zwitterion and a nonfluorescent lactone. Tuning this equilibrium toward the nonfluorescent lactone form can improve cell-permeability and allow creation of "fluorogenic" compounds-ligands that shift to the fluorescent zwitterion upon binding a biomolecular target. An archetype fluorogenic dye is the far-red tetramethyl-Si-rhodamine (SiR), which has been used to create exceptionally useful labels for advanced microscopy. Here, we develop a quantitative framework for the development of new fluorogenic dyes, determining that the lactone-zwitterion equilibrium constant (
Zheng, Q., Ayala, A., Chung, I., Weigel, A., Ranjan, A., Falco, N., Grimm, J., Tkachuk, A., Wu, C., Lippincott-Schwartz, J., Singer, R., & Lavis, L. (2019). Rational Design of Fluorogenic and Spontaneously Blinking Labels for Super-Resolution Imaging.. ACS Cent Sci, 5 (9). http://dx.doi.org/10.1021/acscentsci.9b00676