Activity-Based Imaging of Acid Ceramidase in Living Cells

Yadira F. Ordóñez, José Luís Abad, Mazen Aseeri, Josefina Casas, Virginie Garcia, Mireia Casasampere, Edward H. Schuchman, Thierry Levade, Antonio Delgado, Gemma Triola, Gemma Fabrias

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

16 Citas (Scopus)

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.

Idioma originalInglés
Páginas (desde-hasta)7736-7742
Número de páginas7
PublicaciónJournal of the American Chemical Society
Volumen141
N.º19
DOI
EstadoPublicada - 15 may. 2019

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Publisher Copyright:
© 2019 American Chemical Society.

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