Direct and rapid cytosolic delivery using cell-penetrating peptides mediated by pyrenebutyrate

ACS Chem Biol. 2006 Jun 20;1(5):299-303. doi: 10.1021/cb600127m.


Intracellular delivery of bioactive molecules using arginine-rich peptides, including oligoarginine and HIV-1 Tat peptides, is a recently developed technology. Here, we report a dramatic change in the methods of internalization for these peptides brought about by the presence of pyrenebutyrate, a counteranion bearing an aromatic hydrophobic moiety. In the absence of pyrenebutyrate, endocytosis plays a major role in cellular uptake. However, the addition of pyrenebutyrate results in direct membrane translocation of the peptides yielding diffuse cytosolic peptide distribution within a few minutes. Using this method, rapid and efficient cytosolic delivery of the enhanced green fluorescent protein (EGFP) was achieved in cells including rat hippocampal primary cultured neurons. Enhancement of bioactivity on the administration of anapoptosis-inducing peptide is also demonstrated. Thus, coupling arginine-rich peptides with this hydrophobic anion dramatically improved their ability to translocate cellular membranes, suggesting the great impact of this approach on exploring and controlling cell function.

Publication types

  • Comparative Study
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Membrane / metabolism
  • Cell Membrane Permeability / physiology*
  • Cytosol / metabolism*
  • Drug Delivery Systems / methods*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Peptides / genetics
  • Peptides / pharmacokinetics*
  • Pyrenes / pharmacokinetics*
  • Time Factors


  • Peptides
  • Pyrenes
  • 1-pyrenebutyrate