Abstract
Cell-penetrating peptides including the trans-activating transcriptional activator (Tat) from HIV-1 have been used as carriers for intracellular delivery of a myriad of cargoes including drugs, molecular probes, DNAs and nanoparticles. Utilizing fluorescence flow cytometry and confocal fluorescence microscopy, we demonstrate that a γ-AApeptide mimetic of Tat (48-57) can cross the cell membranes and enter the cytoplasm and nucleus of cells, with efficiency comparable to or better than that of Tat peptide (48-57). Deletion of the four side chains of the γ-AApeptide attenuates translocation capability. We also establish that the γ-AApeptide is even less toxic than the Tat peptide against mammalian cells. In addition to their low toxicity, γ-AApeptides are resistant to protease degradation, which may prove to be advantageous over α-peptides for further development of molecular transporters for intracellular delivery.
Original language | English |
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Pages (from-to) | 1529-1534 |
Number of pages | 6 |
Journal | Molecular Pharmaceutics |
Volume | 9 |
Issue number | 5 |
DOIs | |
State | Published - May 7 2012 |
Externally published | Yes |
Keywords
- Tat
- cell penetrating peptide (CPP)
- cellular uptake
- peptidomimetics
- γ-AApeptides