Academic Journal
Bioorthogonal Tools for Ethanolamine Lipids and Protein Conjugates.
| Τίτλος: | Bioorthogonal Tools for Ethanolamine Lipids and Protein Conjugates. |
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| Συγγραφείς: | Cho YT; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, USA.; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA., Jao CY; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA., Xia Z; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, USA.; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA., White-Mathieu BM; Department of Chemistry, University of New Hampshire, Durham, New Hampshire, USA., Salic A; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA., Baskin JM; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, USA.; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York, USA. |
| Πηγή: | Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2026 Sep 28; Vol. 65 (40), pp. e1866870. Date of Electronic Publication: 2026 Aug 06. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 0370543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3773 (Electronic) Linking ISSN: 14337851 NLM ISO Abbreviation: Angew Chem Int Ed Engl Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2004-> : Weinheim : Wiley-VCH Original Publication: Weinheim/Bergstr. : New York, : Verlag Chemie ; Academic Press, c1962- |
| Ιατρικοί όροι (MeSH): | Ethanolamine*/chemistry , Ethanolamine*/metabolism , Phosphatidylethanolamines*/chemistry , Phosphatidylethanolamines*/metabolism, Alkynes/chemistry ; Azides/chemistry ; Glycosylphosphatidylinositols/chemistry ; Copper/chemistry ; Ubiquitin/chemistry ; Ubiquitin/metabolism ; Click Chemistry ; Cycloaddition Reaction |
| Περίληψη: | Phosphatidylethanolamine (PE) is the second most abundant class of phospholipids in eukaryotic membranes, as well as a precursor for essential posttranslational protein modifications, such as PE conjugates of ubiquitin and ATG8/LC3 that play key roles in autophagy, and glycosylphosphatidylinositol (GPI) anchors of numerous cell surface proteins. Bioorthogonal chemistry has revolutionized how phospholipid biosynthesis, transport, and turnover are studied, with clickable metabolic precursors now available for several phospholipid classes. Yet no metabolic bioorthogonal probe for labeling endogenous PE and PE-derived protein modifications has been developed. Here, we introduce an alkyne-tagged ethanolamine analog (AlkEA) that is incorporated into PE via the Kennedy pathway and can be derivatized by copper-catalyzed azide-alkyne cycloaddition (CuAAC) for visualization and affinity enrichment. Confocal microscopy revealed the subcellular distribution of AlkEA-labeled PE in the ER, Golgi, mitochondria, and autophagosomes, while lipidomic analysis demonstrated AlkEA incorporation across diverse PE species. AlkEA labeling also allowed affinity isolation of PE-conjugated LC3 and ubiquitin, as well as that of a prototypical GPI-anchored protein. AlkEA is thus a minimally perturbing tool broadly applicable to dissecting PE metabolism and PE-dependent protein modifications. (© 2026 The Author(s). Angewandte Chemie International Edition published by Wiley‐VCH GmbH.) |
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| Grant Information: | R35 GM153357 United States GM NIGMS NIH HHS; F32 GM134632 United States GM NIGMS NIH HHS; Ono Pharma Foundation; R35GM153357 United States NH NIH HHS; R35 GM163777 United States GM NIGMS NIH HHS; R35GM163777 United States NH NIH HHS; F32GM134632 United States NH NIH HHS |
| Contributed Indexing: | Keywords: bioorthogonal chemistry; click chemistry; imaging; lipid metabolism; lipidation; phospholipids |
| Substance Nomenclature: | 5KV86114PT (Ethanolamine) 0 (Alkynes) 0 (Phosphatidylethanolamines) 0 (Azides) 0 (Glycosylphosphatidylinositols) 39382-08-6 (phosphatidylethanolamine) 789U1901C5 (Copper) 0 (Ubiquitin) |
| Entry Date(s): | Date Created: 20260806 Date Completed: 20260928 Latest Revision: 20260928 |
| Update Code: | 20260928 |
| PubMed Central ID: | PMC13520642 |
| DOI: | 10.1002/anie.1866870 |
| PMID: | 42559864 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1521-3773 |
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| DOI: | 10.1002/anie.1866870 |