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Conjugation of a Novel Apaf-1 Inhibitor to Peptide-based Cell-Membrane Transporters. Effective Methods to Improve Inhibition of Mitochondria-Mediated Apoptosis

AutorOrzáez, Mar; Mondragón Martínez, Laura; Marzo, Isabel; Sanclimens Pérez de Rozas, Gloria; Messeguer Peypoch, Ángel; Pérez-Payá, Enrique ; Vicent, María J.
Palabras claveApoptosis
Apoptosome inhibitors
Cell-penetrating peptides
Drug delivery systems
Conformational analysis
Membrane mimetics
Fecha de publicaciónmay-2007
EditorElsevier
CitaciónPeptides 28 (5): 958-968
ResumenWe have identified a family of peptoids that inhibits in vitro the activity of the apoptosome, a macromolecular complex that activates mitochondrial-dependent apoptosis pathways. The analysis of peptide-based cell compatible delivery systems of the most active peptoid is presented. The active peptoid was then fused to cell penetrating peptides (CPP) as penetratin (PEN-peptoid) and HIV-1 TAT (TAT-peptoid). PEN-peptoid showed greater cell viability and as a consequence better efficiency as an apoptosis inhibitor than the TAT-peptoid. The intracellular trafficking of both inhibitors was studied by flow cytometry and confocal fluorescence microscopy. Finally, the influence of the cargo (peptoid) molecules on the conformational behavior of the CPP in buffers and in membrane mimetic environments was analyzed using circular dichroism (CD) spectroscopy.
DescripciónThe definitive verison is available at http://www.sciencedirect.com/science//journal/01969781
URIhttp://hdl.handle.net/10261/4330
DOI10.1016/j.peptides.2007.02.014
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