English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/12153
Compartir / Impacto:
Estadísticas
Add this article to your Mendeley library MendeleyBASE
Citado 53 veces en Web of Knowledge®  |  Pub MebCentral Ver citas en PubMed Central  |  Ver citas en Google académico
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Título

Small molecule inhibitors of Apaf-1-related caspase-3/-9 activation that control mitochondrial-dependent apoptosis

AutorMalet Engra, Gema; Martín, A. G.; Orzáez, Mar; Vicent, María J.; Masip, Isabel; Sanclimens Pérez de Rozas, Gloria; Ferrer-Montiel, Antonio; Mingarro, Ismael; Messeguer Peypoch, Ángel; Fearnhead, H. O.; Pérez-Payá, Enrique
Palabras claveApoptosis
Apoptosome
Apaf-1
Caspasa-3
Caspasa-9
Combinatorial libraries inhibitor
Molecular recognition
Peptoid
Protein-protein interactions
Small molecule
Fecha de publicación2006
EditorNature Publishing Group
CitaciónCell Death & Differentiation 13(9): 1523-1532 (2006)
ResumenApoptosis is a biological process relevant to human disease states that is strongly regulated through protein–protein complex formation. These complexes represent interesting points of chemical intervention for the development of molecules that could modulate cellular apoptosis. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated Apaf-1 (apoptotic protease-activating factor), dATP and procaspase-9 that link mitochondria disfunction with activation of the effector caspases and in turn is of interest for the development of apoptotic modulators. In the present study we describe the identification of compounds that inhibit the apoptosome-mediated activation of procaspase-9 from the screening of a diversity-oriented chemical library. The active compounds rescued from the library were chemically optimised to obtain molecules that bind to both recombinant and human endogenous Apaf-1 in a cytochrome c-noncompetitive mechanism that inhibits the recruitment of procaspase-9 by the apoptosome. These newly identified Apaf-1 ligands decrease the apoptotic phenotype in mitochondrial-mediated models of cellular apoptosis.
Descripción10 pages, 5 figures.-- PMID: 16341125 [PubMed].-- Available online Dec 9, 2005.
Supporting information available at: http://www.nature.com/cdd/journal/v13/n9/suppinfo/4401828s1.html?url=/cdd/journal/v13/n9/abs/4401828a.html
Versión del editorhttp://dx.doi.org/10.1038/sj.cdd.4401828
URIhttp://hdl.handle.net/10261/12153
DOI10.1038/sj.cdd.4401828
ISSN1350-9047 (Print)
1476-5403 (Online)
Aparece en las colecciones: (IQAC) Artículos
(IBV) Artículos
Ficheros en este ítem:
No hay ficheros asociados a este ítem.
Mostrar el registro completo
 



NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.