Development of background-free tame fluorescent probes for intracellular live cell imaging

Samira Husen Alamudi, Rudrakanta Satapathy, Jihyo Kim, Dongdong Su, Haiyan Ren, Rajkumar Das, Lingna Hu, Enrique Alvarado-Martínez, Jung Yeol Lee, Christian Hoppmann, Eduardo Peña-Cabrera, Hyung-Ho Ha, Hee-Sung Park (), Lei Wang () and Young-Tae Chang ()
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Samira Husen Alamudi: National University of Singapore
Rudrakanta Satapathy: National University of Singapore
Jihyo Kim: Korea Advanced Institute of Science and Technology
Dongdong Su: Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science, Technology and Research
Haiyan Ren: University of California
Rajkumar Das: National University of Singapore
Lingna Hu: National University of Singapore
Enrique Alvarado-Martínez: Universidad de Guanajuato
Jung Yeol Lee: National University of Singapore
Christian Hoppmann: University of California
Eduardo Peña-Cabrera: Universidad de Guanajuato
Hyung-Ho Ha: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University
Hee-Sung Park: Korea Advanced Institute of Science and Technology
Lei Wang: University of California
Young-Tae Chang: National University of Singapore

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule’s roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky. Here we report the first predictive model for cell permeable background-free probe development through optimized lipophilicity, water solubility and charged van der Waals surface area. The model was developed by utilizing high-throughput screening in combination with cheminformatics. We demonstrate its reliability by developing CO-1 and AzG-1, a cyclooctyne- and azide-containing BODIPY probe, respectively, which specifically label intracellular target organelles and engineered proteins with minimum background. The results provide an efficient strategy for development of background-free probes, referred to as ‘tame’ probes, and novel tools for live cell intracellular imaging.

Date: 2016
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DOI: 10.1038/ncomms11964

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