Harnessing Clickable Acylated Glycerol Probes As Chemical Tools for Tracking Glycerolipid Metabolism

Overview

Journal Chemistry

Specialty Chemistry

Date 2023 Apr 22

PMID 37085958

Authors

Christelle F Ancajas

Adam J Carr

Jinchao Lou

Ruhani Sagar

Yue Zhou

Todd B Reynolds

Michael D Best

Affiliations

Soon will be listed here.

Abstract

We report the use of clickable monoacylglycerol (MAG) analogs as probes for the labeling of glycerolipids during lipid metabolism. Incorporation of azide tags onto the glycerol region was pursued to develop probes that would label glycerolipids, in which the click tag would not be removed through processes including acyl chain and headgroup remodeling. Analysis of clickable MAG probes containing acyl chains of different length resulted in widely variable cell imaging and cytotoxicity profiles. Based on these results, we focused on a probe bearing a short acyl chain (C -MAG-N ) that was found to infiltrate natural lipid biosynthetic pathways to produce click-tagged versions of both neutral and phospholipid products. Alternatively, strategic blocking of the glycerol sn-3 position in probe C -MEG-N served to deactivate phospholipid tagging and focus labeling on neutral lipids. This work shows that lipid metabolic labeling profiles can be tuned based on probe structures and provides valuable tools for evaluating alterations to lipid metabolism in cells.

Citing Articles

Probing Glycerolipid Metabolism using a Caged Clickable Glycerol-3-Phosphate Probe.

Lou J, Ancajas C, Zhou Y, Lane N, Reynolds T, Best M Chembiochem. 2024; 25(18):e202300853.

PMID: 38705850 PMC: 11535253. DOI: 10.1002/cbic.202300853.

The small molecule CBR-5884 inhibits the phosphatidylserine synthase.

Zhou Y, Phelps G, Mangrum M, McLeish J, Phillips E, Lou J mBio. 2024; 15(5):e0063324.

PMID: 38587428 PMC: 11077991. DOI: 10.1128/mbio.00633-24.

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