Cell-penetrating peptides : types and mechanisms of penetration

Abstract

Before discovery of the Tat peptide over twenty years ago, it was assumed that large peptides and proteins do not penetrate cell membranes. After discovery of Tat, Penetratin [1, 2] and several other peptides of natural origin, able to cross the cell membranes in an energy-independent manner, the structural determinants of their cell-penetrating potency were established, including polycationic character, amphipaticity and presence of proline-rich motifs [3, 4]. Currently known cell-penetrating peptides of natural or synthetic origin are composed of 5 to 40 amino acid residues and belong to one of the three families: oligocationic, amphipatic or proline-rich and penetrate the biological membranes by endocytosis or other ways of direct translocation. Most of these translocation mechanisms are not exclusive and may occur simultaneously, and their contribution may be different for each peptide depending on the conditions (e.g. CPP concentration, pH, etc.). Most CPPs demonstrate little or no mammalian cell toxicity what makes them promising vectors for drug delivery. Such vectors might be useful for efficient internalization of compounds otherways poorly penetrating biological membranes. Novel CPP-effector conjugates may become effective anticancer or antimicrobial agents of a great potential for chemotherapy [3, 5]. In this short review we present a glimpse at the current state of knowledge concerning sub‑families, types and mechanisms of action of most prominent members of CPP family