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Issue 11, 2014
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Peptide targeting of fluorescein-based sensors to discrete intracellular locales

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Abstract

Fluorescein-based sensors are the most widely applied class of zinc probes but display adventitious localization in live cells. We present here a peptide-based localization strategy that affords precision in targeting of fluorescein-based zinc sensors. By appending the zinc-selective, reaction-based probe Zinpyr-1 diacetate (DA-ZP1) to the N-terminus of two different targeting peptides we achieve programmable localization and avoid unwanted sequestration within acidic vesicles. Furthermore, this approach can be generalized to other fluorescein-based sensors. When appended to a mitochondrial targeting peptide, the esterase-activated profluorophore 2′,7′-dichlorofluorescein diacetate can be used effectively at concentrations four-times lower than previously reported for analogous, non-acetylated derivatives. These results demonstrate on-resin or in-solution esterification of fluorescein to be an effective strategy to facilitate peptide-based targeting in live cells.

Graphical abstract: Peptide targeting of fluorescein-based sensors to discrete intracellular locales

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Publication details

The article was received on 03 May 2014, accepted on 18 Jul 2014 and first published on 12 Aug 2014


Article type: Edge Article
DOI: 10.1039/C4SC01280A
Author version available: Download Author version (PDF)
Citation: Chem. Sci., 2014,5, 4512-4516
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    Peptide targeting of fluorescein-based sensors to discrete intracellular locales

    R. J. Radford, W. Chyan and S. J. Lippard, Chem. Sci., 2014, 5, 4512
    DOI: 10.1039/C4SC01280A

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