Cell-penetrating peptides characteristic

Identifying a cell-specific peptide with cell-penetrating characteristics is not always an easy task. The major drawback of conventional CPPs, such as TAT from HTV-TAT (Vives et al., 1997) and penetratin from the Antennapedia homeodomain (Derossi et al., 1994) are their lack of cell specificity, hampering their clinical development (Vives et al., 2008). 

Anti-deoxyribonucleic acid autoantibodies from human and mice suffering from Lupus erythematosus can penetrate into cells and accumulate in the cell nucleus. Based on the characteristics of a mi-ON A autoantibodies, VAYISRGGVSTYYSDTVKGRFTRQKYNKRA peptide (P3), which exhibits a-helix, has been used as a vector for the intracytoplasmic and intranuclear translocation of macromolecules (Table 16.7) (Avrameas et al., 1998, 1999). P3 shares similar capabilities with Antenapedia peptide (Derossi et al., 1994), but in contrast P3 operates only at 37 °C by an energy dependent mechanism. P3 linked to a 19 lysine residue sequence (K19-P3) forms complexes with plasmid DNA. Efficient transfection of mouse 3T3 cells and hamster lung CCL39 cells were obtained with these complexes. This transfection was not impaired by the presence of serum and did not require helper molecules such as chloroquine. These observations suggest that peptides from cell specific anti-DNA autoantibodies may represent a source of peptide-based gene delivery system with different specificities. 

Peptide-hormones like hypothalamus-pituitary, gastrointestinal, parathyroid, neurohormones, Gfs related peptide-hormones cannot penetrate the plasma membrane and their receptors are located on the cell surface and the signal transport to the nucleus is becoming via a second messenger. The main hormone action seems to be DNA synthesis whereas other including mediation of neurotransmission, enzyme synthesis, regulation and synthesis of structural proteins are responsible for the specific characteristics of differentiated cell. 

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