Journal
CHEMICAL SCIENCE
Volume 5, Issue 11, Pages 4512-4516Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4sc01280a
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Funding
- NIH from the National Institute of General Medical Sciences [GM065519]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM065519] Funding Source: NIH RePORTER
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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.
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