The definitive verison is available at http://www.sciencedirect.com/science//journal/01969781
We 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.
This work was supported by grants from Spanish Ministry of Science and Education (MEC) (BIO2004-998 and CTQ2005-00995), Fundación Centro de Investigación Príncipe Felipe and a Marie Curie Reintegration grant (MERG-2004-06307). Mar Orzáez thanks Bancaja for a postdoctoral fellowship. Laura Mondragón is supported by a FPI fellowship from MEC. The confocal microscope was supported by MEC through FEDER.
Peer reviewed