Cellular translocation of a γ-AApeptide mimetic of Tat peptide

Mol Pharm. 2012 May 7;9(5):1529-34. doi: 10.1021/mp300070w. Epub 2012 Apr 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell-Penetrating Peptides
  • Flow Cytometry
  • Humans
  • Microscopy, Confocal
  • Peptide Fragments / chemistry*
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Protein Transport
  • tat Gene Products, Human Immunodeficiency Virus / chemistry*


  • Cell-Penetrating Peptides
  • Peptide Fragments
  • Peptides
  • tat Gene Products, Human Immunodeficiency Virus
  • tat peptide (48-57), Human immunodeficiency virus 1