Issue 11, 2017

Michael addition-based probes for ratiometric fluorescence imaging of protein S-depalmitoylases in live cells and tissues

Abstract

The reversible modification of cysteine residues through thioester formation with palmitate (protein S-palmitoylation) is a prevalent chemical modification that regulates the function, localization, and stability of many proteins. Current methods for monitoring the “erasers” of S-palmitoylation, acyl-protein thioesterases (APTs), rely on destructive proteomic methods or “turn-on” probes, precluding deployment in heterogeneous samples such as primary tissues. To address these challenges, we present the design, synthesis, and biological evaluation of Ratiometric Depalmitoylation Probes (RDPs). RDPs respond to APTs with a robust ratiometric change in fluorescent signal both in vitro and in live cells. Moreover, RDPs can monitor endogenous APT activities in heterogeneous primary human tissues such as colon organoids, presaging the utility of these molecules in uncovering novel roles for APTs in metabolic regulation.

Graphical abstract: Michael addition-based probes for ratiometric fluorescence imaging of protein S-depalmitoylases in live cells and tissues

Associated articles

Supplementary files

Article information

Article type
Edge Article
Submitted
23 Jun 2017
Accepted
09 Sep 2017
First published
11 Sep 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 7588-7592

Michael addition-based probes for ratiometric fluorescence imaging of protein S-depalmitoylases in live cells and tissues

Michael W. Beck, R. S. Kathayat, C. M. Cham, E. B. Chang and B. C. Dickinson, Chem. Sci., 2017, 8, 7588 DOI: 10.1039/C7SC02805A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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