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Título: | Activity-Based Imaging of Acid Ceramidase in Living Cells |
Autor: | Ordóñez, Yadira F.; Abad, José Luis CSIC ORCID ; Aseeri, Mazen; Casas, Josefina CSIC ORCID ; Garcia, Virginie; Casasampere, Mireia CSIC ORCID; Schuchman, Edward H.; Levade, Thierry; Delgado Cirilo, Antonio CSIC ORCID; Triola Guillem, Gemma CSIC ORCID; Fabriàs, Gemma CSIC ORCID | Palabras clave: | Cells Acid ceramidase Ceramides Alzheimer’s disease Cancer |
Fecha de publicación: | 28-abr-2019 | Editor: | American Chemical Society | Citación: | Journal of the American Chemical Society 2019 | Resumen: | Acid ceramidase (AC) hydrolyzes ceramides into sphingoid bases and fatty acids. The enzyme is overexpressed in several types of cancer and Alzheimer’s disease, and its genetic defect causes different incurable disorders. The availability of a method for the specific visualization of catalytically active AC in intracellular compartments is crucial for diagnosis and follow-up of therapeutic strategies in diseases linked to altered AC activity. This work was undertaken to develop activity-based probes for the detection of AC. Several analogues of the AC inhibitor SABRAC were synthesized and found to act as very potent (two-digit nM range) irreversible AC inhibitors by reaction with the active site Cys143. Detection of active AC in cell-free systems was achieved either by using fluorescent SABRAC analogues or by click chemistry with an azide-substituted analogue. The compound affording the best features allowed the unprecedented labeling of active AC in living cells. | Versión del editor: | https://pubs.acs.org/doi/full/10.1021/jacs.8b11687 | URI: | http://hdl.handle.net/10261/181017 | DOI: | 10.1021/jacs.8b11687 |
Aparece en las colecciones: | (IQAC) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
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Activity-Based Imaging of Acid Ceramidase in Living Cells.docx | Artículo principal | 1,93 MB | Microsoft Word XML | Visualizar/Abrir |
Activity Based Imaging of Acid Ceramidase in Living Cells. Supporting information.docx | Material suplementario | 3,08 MB | Microsoft Word XML | Visualizar/Abrir |
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