Peptide targeting of fluorescein-based sensors to discrete intracellular locales
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Lippard_Peptide targeting.pdf
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719.12 KB
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Checksum (MD5)
24981a0205ad9aac49aeb9107294d02b
Author(s)
Radford, Robert John
Chyan, Wen
Lippard, Stephen J.
Date Issued
August 2014
Journal
Chemical Science
Publisher
Royal Society of Chemistry
Citation
Radford, Robert J., Wen Chyan, Stephen J. Lippard. "Peptide targeting of fluorescein-based sensors to discrete intracellular locales." Chemical Science, 2014, 5, 4512-4516.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1039/c4sc01280a
