Sources that classify based on origin break it up into three classes: CPPs derived from proteins, chimeric peptide CPPs, and synthetic CPPs (Bechara and Sagan, Bolhassani and Rafati, Pooga, et al.). When classifying based on physico-chemical characteristics there are again usually three classes but also some that don’t quite fit into the three main groups (Deshayes et al., Shi et al., Koren and Torchilin, Farkhani et al.). The first group is that of the cationic CPPs or also known as low amphipathic and include TAT, penetratin, P22N, otcaarginine(R8), etc. The second group are the amphipathic CPPs including transportan, MAP, CADY, etc. The third group is charged and hydrophobic CPPs which include MPG peptides, K-FGF, C105Y, and vascular endothelial-cadherin (pVEC). The subgroups of this classification are proline-rich and antimicrobial peptides as well as a subgroup of CPPs containing a combination of the previous groups although some classification systems will include the subgroups within the three main groups. In addition there are yet other CPPs known as the pH responsive, such as H7K (R2)2, and activable CPPs (ACCP) which involve proteolysis of a linker between domains. (Deshayes et al., Shi et al., Koren and Torchilin, Farkhani et …show more content…
It was discovered independently by two different scientific groups, Frankel and Pabo and Green and Loewenstein, in 1988 (Koren and Torchilin, Huang et al., Dupont et al.). The complete TAT protein of HIV-1 has three domains consisting of 101 amino acid residues. Just as its name implies, there is a domain responsible for transactivation activity and makes up the N-terminal region, a domain that is cysteine rich and binds DNA, and a domain similar to nuclear localization sequence that is basic in nature and was discovered to hold the minimal peptide sequence required for membrane translocation (Deshayes et al., Jeang et al.). The typical cargo of TAT has been oligonucleotides, but also includes other nucleic acids and fusion proteins. Other vectors can harness the membrane crossing abilities of TAT by associating the CPP on the surface of the vector. TAT conjugates are usually formed through covalent interactions with the cargo and transfection can be improved when di- or trimers of TAT are used (Deshayes et al.). The mechanism for crossing the cell membrane appears to be by caveolae/lipid raft-mediated endocytosis, macropinocytosis dependent upon lipid rafts, or clathrin mediated endocytosis (Deshayes et al., Koren and Torchilin). TAT has the unique ability to transfect neighboring cells which is very beneficial when trying to transfect numerous cells such