HIV TAT (48-60) GRKKRRQRRRPPQ-NH2 (amide)

Cell penetrating peptide (CPPs) are characterised by their ability to promote the receptor-independent cellular uptake of membrane-impermeable macromolecules, such as peptides, proteins, nucleic acids and nanoparticles. CPPs are usually short peptides with less than 30 amino acids. They are mostly amphipathic and highly cationic and usually rich of the amino acids arginine and lysine. Cellular internalisation of CPPs is observed for virtually all cells, although with different efficiencies that depend on the CPP, the cargo and the cell type (Verdurmen and Brock 2011, Trends Pharmacol. Sci. 32, 116-124).

In 1988 the first CPP, the HIV-1 Trans-Activator of Transcription (TA) protein was discovered independently by two laboratories. In 1991, the 60 amino acid Antennopedia homeodomain peptide was shown to enter nerve cells. Three years later it was reported, that a 16 mer peptide corresponding to the third helix of homeodomainis, Antennopedia (43-58) > is capable to translocate through cell membranes.