Peptide targeting of fluorescein-based sensors to discrete intracellular locales
Author(s)Radford, Robert John; Chyan, Wen; Lippard, Stephen J.
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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.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Royal Society of Chemistry
Radford, Robert J., Wen Chyan, Stephen J. Lippard. "Peptide targeting of fluorescein-based sensors to discrete intracellular locales." Chemical Science, 2014, 5, 4512-4516.
Author's final manuscript