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 Penã-Cabrera, Hyung Ho Ha, Hee Sung Park, Lei Wang, Young Tae Chang

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)

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.

Original languageEnglish
Article number11964
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 20 Jun 2016

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