Journal
PEPTIDES
Volume 28, Issue 5, Pages 958-968Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2007.02.014
Keywords
apoptosis; apoptosome inhibitors; cell-penetrating peptides; drug delivery systems; conformational analysis; membrane mimetics
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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. (c) 2007 Elsevier Inc. All rights reserved.
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