New fluorogenic probes for neutral and alkaline ceramidases

New fluorogenic ceramidase substrates derived from the N acyl modification of our previously reported probes (RBM14) are reported. While none of the new probes were superior to the known RBM14C12 as acid ceramidase substrates, the corresponding nervonic acid amide (RBM14C24:1) is an efficient and se...

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Detalles Bibliográficos
Autores: Casasampere, Mireia, Bielsa, Núria, Riba, Daniel, Bassas, Laura, Ruijuan, Xu, Cungui, Mao, Fabriàs, Gemma, Abad, José Luis, Delgado Cirilo, Antonio, Casas, Josefina
Tipo de recurso: artículo
Estado:Versión enviada para evaluación y publicación
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/179544
Acceso en línea:http://hdl.handle.net/10261/179544
Access Level:acceso abierto
Palabra clave:Cancer
Ceramides
Lipids
Ceramidases
Lipase
Fluorogenic
Substrate
Chemical synthesis
Descripción
Sumario:New fluorogenic ceramidase substrates derived from the N acyl modification of our previously reported probes (RBM14) are reported. While none of the new probes were superior to the known RBM14C12 as acid ceramidase substrates, the corresponding nervonic acid amide (RBM14C24:1) is an efficient and selective substrate for the recombinant human neutral ceramidase, both in cell lysates and in intact cells. A second generation of substrates, incorporating the natural 2 (N acylamino) 1,3 diol 4 ene framework (compounds RBM15) is also reported. Among them, the corresponding fatty acyl amides with an unsaturated N acyl chain can be used as substrates to determine ACER1 and ACER2 activities. In particular, compound RBM15C18:1 has emerged as the best fluorogenic probe reported so far to measure ACER1 and ACER2 activities in a 96 well plate format.