Cell-penetrating peptides (CPPs) have been used to overcome the lipophilic barrier of the cellular membranes of mammalian cells because of the ability to cross the plasma membranes in an apparently energy- and receptor-independent manner. There is much controversy over the mechanism by which this 'cell penetration' occurs, nonetheless, the ability of CPPs to penetrate rapidly into cells is being used to deliver various cargoes such as proteins, DNA, antibodies, oligonucleotides, nanoparticles, including liposomes in a variety of situations and biological systems for their biological actions.Here, we report a novel cell-penetrating peptide of the third helix of the 30Kc19 protein that has the ability to penetrate into mammalian cells and also has the capability to deliver cell-impermeable cargos into mammalian cells in a relatively efficient manner like other CPPs with less cytotoxicity. We have successfully identified the most optimal domain that enables penetration of the 30Kc19 protein; 30Kc19 CPP, and in this process, we have observed a special character of this specific CPP that penetrates into cells not like the rest of other known CPPs, but rather by homodimerization mechanism at the plasma membrane prior to penetration which remains as dimer form inside the cell. We believe this newly discovered CPP has the potential therapeutic applications in a wide range of areas such as in drug delivery, gene transfer and beyond.

Novel cell-penetrating peptide of the third helix of the 30Kc19 protein that homodimerizes upon penetration for efficient intracellular delivery of therapeutics

244th National Meeting (2012)

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