Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Apoptosis / drug effects*
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Apoptosomes / antagonists & inhibitors
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Apoptotic Protease-Activating Factor 1 / antagonists & inhibitors*
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Carrier Proteins / chemistry
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Cell Line
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Cell Line, Tumor
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Cell Survival / drug effects
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Cell-Penetrating Peptides
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Circular Dichroism
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Flow Cytometry
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Gene Products, tat / chemistry
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Humans
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Microscopy, Confocal
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Molecular Sequence Data
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Molecular Structure
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Peptides / chemistry
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Peptides / pharmacokinetics
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Peptides / pharmacology*
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Peptoids / chemistry
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Peptoids / pharmacokinetics
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Peptoids / pharmacology*
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Protein Conformation
Substances
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APAF1 protein, human
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Apoptosomes
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Apoptotic Protease-Activating Factor 1
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Carrier Proteins
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Cell-Penetrating Peptides
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Gene Products, tat
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Peptides
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Peptoids
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penetratin