A Closer Look at Protein Transduction Domains as a Tool in Drug Delivery

New drug delivery technologies have an important niche in treatments as they enable drugs to be more effective. Remarkably, drug delivery is still considered a poor relation to drug discovery with greater than 95% of all new potential therapeutics having poor pharmacokinetics. The greatest obstruction for cytosolic release of therapeutic molecules is the membrane barrier of target cells. The use of protein transduction domains (PTD), capable of transporting effector molecules, such as compounds, proteins and DNA, into cells has become increasingly attractive in the design of drugs as they promote the cellular uptake of cargo molecules. The PTDs are also often referred to as Trojan peptides, membrane translocating sequences or cell permeable proteins. They are generally 10-16 amino acids in length. The mechanism of internalisation remains unclear, however, recent evidence supports an energy dependant process involving endocytosis. PTDs may be grouped according to their composition, for example peptides rich in arginine and/or lysine (Tat protein from HIV-1), or secondary structure, for example α-helix (HA2 from influenza virus hemagglutinin) and β- sheet (protegrins derived from antimicrobial peptides).