title: Peptide Targeting of Fluorescein-Based Sensors to Discrete Intracellular Locales.
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.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Radford
authors.forename: Wen
authors.initials: W
authors.lastname: Chyan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard