A Small Molecule Fluorogenic Probe for the Detection of Sphingosine in Living Cells

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Oct 12

PMID 33044062

Citations 5

Authors

Andrew K Rudd

Neel Mittal

Esther W Lim

Christian M Metallo

Neal K Devaraj

Affiliations

Soon will be listed here.

Abstract

The single-chained sphingolipid sphingosine is an essential structural lipid and signaling molecule. Abnormal sphingosine metabolism is observed in several diseases, including cancer, diabetes, and Alzheimer's. Despite its biological importance, there is a lack of tools for detecting sphingosine in living cells. This is likely due to the broader challenge of developing highly selective and live-cell compatible affinity probes for hydrophobic lipid species. In this work, we have developed a small molecule fluorescent turn-on probe for labeling sphingosine in living cells. We demonstrate that this probe exhibits a dose-dependent response to sphingosine and is able to detect endogenous pools of sphingosine. Using our probe, we successfully detected sphingosine accumulation in cells from patients with Niemann-Pick type C1 (NPC1), a lipid transport disorder in which increased sphingosine mediates disease progression. This work provides a simple and accessible method for the detection of sphingosine and should facilitate study of this critical signaling lipid in biology and disease.

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