Uptake of analogs of penetratin, Tat(48-60) and oligoarginine in live cells

Biochem Biophys Res Commun. 2003 Jul 18;307(1):100-7. doi: 10.1016/s0006-291x(03)01135-5.


Cell-penetrating peptides are regarded as promising vectors for intracellular delivery of large, hydrophilic molecules, but their mechanism of uptake is poorly understood. Since it has now been demonstrated that the use of cell fixation leads to artifacts in microscopy studies on the cellular uptake of such peptides, much of what has been considered as established facts must be reinvestigated using live (unfixed) cells. In this work, the uptake of analogs of penetratin, Tat(48-60), and heptaarginine in two different cell lines was studied by confocal laser scanning microscopy. For penetratin, an apparently endocytotic uptake was observed, in disagreement with previous studies on fixed cells found in the literature. Substitution of the two tryptophan residues, earlier reported to be essential for cellular uptake, did not alter the uptake characteristics. A heptaarginine peptide, with a tryptophan residue added in the C-terminus, was found to be internalized by cells via an energy-independent, non-endocytotic pathway. Finally, a crucial role for arginine residues in penetratin and Tat(48-60) was demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell-Penetrating Peptides
  • Cricetinae
  • Fluorescent Dyes / metabolism
  • Gene Products, tat / chemistry
  • Gene Products, tat / metabolism*
  • Microscopy, Confocal
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Rats
  • tat Gene Products, Human Immunodeficiency Virus


  • Carrier Proteins
  • Cell-Penetrating Peptides
  • Fluorescent Dyes
  • Gene Products, tat
  • Oligopeptides
  • Peptide Fragments
  • heptaarginine amide
  • tat Gene Products, Human Immunodeficiency Virus
  • tat peptide (48-60), Human immunodeficiency virus 1
  • penetratin