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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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Supplementary files

Article information


Submitted
03 May 2014
Accepted
18 Jul 2014
First published
12 Aug 2014

Chem. Sci., 2014,5, 4512-4516
Article type
Edge Article
Author version available

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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