Cell Penetrating Peptides

Cell-penetrating peptides (CPPs) are relatively short peptides, which when covalently bound to large molecules have the ability to transport them through cell walls and into the cytoplasm. A difficulty in delivering biologically active molecules for therapeutic applications or as biological probes is to overcome hydrophobic and almost impermeable permeable cell barriers. CPPs can transport a wide variety of conjugated molecules into cells - peptides, fluorophores, organic substrates, toxins, drugs, proteins and DNA.

CPPs can be categorized into three main classes - cationic, amphipathic, and hydrophobic peptides.

The cationic class of CPPs have highly positive net charges at physiological pH that primarily originates from the basic short strands of arginines and lysines. Peptides belonging to this class include TAT-derived peptides, penetratin and polyarginines.

Amphipathic CPPs contain both polar and nonpolar regions of amino acids. They are also rich in hydrophobic residues, such as valine, leucine, isoleucine, and alanine. Amphipathic peptides are generally classified into primary, secondary, and proline-rich CPPs. 

Hydrophobic CPPs mainly contain nonpolar residues, resulting in a low net charge. These hydrophobic motifs are crucial for the process of cellular internalization.

Medical application of CPPs has been used for the delivery of various types of therapeutic molecules, such as antimicrobial, anti-inflammatory, antineoplastic, and neuroprotective agents.