CPP9 – Cell Penetrating Peptides – CPP

CPP9 is a small, amphipathic, cyclic peptide which is a highly efficient cell penetrating peptide (CPP). CPP9 binds directly to the plasma membrane phospholipids and enters mammalian cells via endocytosis. CPP9 is then efficiently released from the endosome. CPP9 is capable of delivering a variety of cargo molecules (such as small-molecule dyes, peptides, and proteins) into the cytosol of mammalian cells with efficiencies 4- to 12-fold higher than that of R9, Tat, and penetratin. This high cytosolic delivery efficiency is due to a vastly improved endosomal escape process. CPP9 exits the endosome by binding to the endosomal membrane and inducing CPP-enriched lipid domains to bud off as small vesicles. Together with the high proteolytic stability of cyclic CPP9, its low cytotoxicity, and oral bioavailability, CPP9 may provide a powerful system for intracellular delivery of therapeutic agents and chemical probes.