2. Academic Validation
  3. Development of background-free tame fluorescent probes for intracellular live cell imaging

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

  • Nat Commun. 2016 Jun 20;7:11964. doi: 10.1038/ncomms11964.
Samira Husen Alamudi 1,  Rudrakanta Satapathy 1,  Jihyo Kim 2,  Dongdong Su 3,  Haiyan Ren 4,  Rajkumar Das 1,  Lingna Hu 1,  Enrique Alvarado-Martínez 5,  Jung Yeol Lee 1,  Christian Hoppmann 4,  Eduardo Peña-Cabrera 5,  Hyung-Ho Ha 6,  Hee-Sung Park 2,  Lei Wang 4,  Young-Tae Chang 1 3
Affiliations

Affiliations

  • 1 Department of Chemistry &Med Chem Program, National University of Singapore, Singapore 117543, Singapore.
  • 2 Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305701, Republic of Korea.
  • 3 Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore 138667, Singapore.
  • 4 Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California San Francisco, California 94158, USA.
  • 5 Departamento de Química, Universidad de Guanajuato, Guanajuato 36050, Mexico.
  • 6 College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon 540950, Republic of Korea.
PMID: 27321135 DOI: 10.1038/ncomms11964
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.

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