Table 1.

Examples of cell-penetrating peptide (CPP) archetypes, origins, sequences, secondary structures and physicochemical classes.

CPP	Origin	Sequence	Physicochemical Class and Secondary Structure
Protein-derived
TAT48-60	Protein of HIV-1	GRKKRRQRRRPQ	cationic random coil (rdc) *
Penetratin (Antp43-68)	Antennapedia homeodomain of D. melanogaster	RQIKIWFQNRRMKWKK	cationic β-strand/rdc *
VP22	Herpes simplex virus type I	NAKTRRHERRRKLAIER	amphipathic α-helix
pVEC	Cadherin615–632	IRKQAHAHSK	amphipathic β-strand/rdc *
Chimeric
Transportan	Galanine/Mastoparan	GWTLNSAGYLLGKINLKALAALAKKIL	amphipathic α-helix *
Pep-1	HIV-reverse transcriptase/SV40 T-antigen	KETWWETWWTEWSQPKKKRKV	amphipathic α-helix *
MPG	HIV-gp41/SV40 T-antigen	GALFLGFLGAAGSTMGAWSQPKKKRKV	amphipathic β-strand/rdc
Synthetic
Polyarginines	Based on Tat peptide	Poly-arginine, (R)n; 6 < n < 12	cationic rdc *
MAP	designed	KLALKLALKALKAALKLA	amphipathic α-helix *
KALA	designed	WEAKLAKALAKALAKHLAKALAKALKACEA	amphipathic α-helix

Note: Examples are based on references [17,19,20]. The mechanisms of membrane translocation and cell entry of these archetypal CPPs are not definitively elucidated. However, distinct mechanisms are involved, such as direct translocation (non-endocytic pathway, like an inverted micelle, pore formation, carpet-like and membrane thinning) and endocytosis-mediated internalization (macropinocytosis, clathrin- and caveolin-dependent endocytosis, clathrin- and caveolin-independent endocytosis and receptor-mediated endocytosis. These CPPs can utilize more than a single route for cell entry [19,20,30]. “*”, as structurally characterized in the presence of negatively charged dioleoylphosphatidylglycerol [26].