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The cellular uptake of biologically active molecules is an important subject in scientific research. While application of cell-penetrating peptides (CPPs, also known as Protein Transduction Domains) for delivering biologically active molecules across cellular membranes into cells is an important breakthrough in cell biology, and the research in this field has gained much attention in recent years. Most CPPs are relatively short peptides that consist of less than 40 amino acids and are able to enter cells through various ways, including endocytosis and energy-independent pathway. Because of strong cell-penetrating capability, CPPs are further able to assist in the intracellular delivery of covalently or non-covalently conjugated bioactive cargos, ranging from small chemical drugs and nanoparticles to large plasmid DNA.

The History of CPPs
Historically, there are several fundamental investigations in CPPs that deserve credit. In 1987, Bienert and his group first illustrated a receptor-independent activation of mast cells by substance P (SP) analogs.

Following these permeation studies, SP sequences were used for uptake studies, and new amphipathic model peptides were developed. In 1988, the cellular uptake of the transactivator of transcription (TAT) from HIV-1 was reported by Frankel and Pabo. Another breakthrough in this area was the discovery of a 60-mer peptide (penetration-Helix 3 of the antennapedia homeodomain) which is able to penetrate the cells of neuronal cultures.

The Classification of CPPs
Since the first CPP transactivator of transcription (TAT) is discovered, plenty of CPPs have been investigated, such as polyarginine peptides, octa arginine nonaarginine, and dodecaarginine. CPPs could be mainly classified into five groups based on their Physical–chemical properties, which are cationic peptides, hydrophobic peptides, amphipathic peptides, proline-rich and antimicrobial peptides, and chimeric peptides. It could also be classified based on their origin or function, such as antennapedia peptides, chimeric peptides, HIV-TAT family peptides, nuclear localization peptides, oligoarginine peptides, etc.

Synthesis of Cell Penetrating Peptides
Creative Peptides is an experienced company that has supplied a variety of CPPs over the years. We have synthesized numerous commonly used CPPs and we also provide special CPPs composed of unusual or non-natural amino acids. Unless otherwise specified, all peptides have >95% purity and contain TFA (trifluoroacetic acid) as counter-ions. If you are interested in the cell-penetrating peptides for your research, please do not hesitate to contact us.

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