Cell-penetrating peptide

A cell-penetrating peptide ( engl. cell- penetrating peptides or protein transduction domain, PTD or CPP ) refers to a peptide that penetrate cell membranes ( penetrate ) can. This also allows an attached to the peptide fusion protein, as well as covalently or non- covalently associated with the cell-penetrating peptide nucleic acids, or nanoparticles, can be introduced into cells. There were also small molecules such as cytotoxic drugs, antivirals, contrast agents or quantum dots placed in cells with cell-penetrating peptides.

The CPP were discovered in 1988 simultaneously by two research groups, as it was found that the Tat protein of human immunodeficiency virus was picked up by various cell types in cell culture. Since then, other examples of the CPP are known. Even with polycationic proteins such as anti- DNA antibody or a recording histones in cells could be shown.

Mechanism

Most of the cell-penetrating peptides consist mainly of non-polar and basic amino acids, especially lysine and arginine, tryptophan, phenylalanine, leucine and isoleucine ( polycationic type). The cationic amino acids bind to the negatively charged receptors on the cell surface, such as sialic acid or heparan sulphate, while the non-polar amino acids mediate the adsorption of the lipids of the cell membrane. Another type consists of alternating polar and non-polar amino acids ( amphipathic type).

Cell-penetrating peptides having different sequences, and there are three hypotheses, such as the cell penetration takes place:

  • Via direct penetration of the cell membrane by pore formation
  • About hygroscopic buffer effects (English proton sponge ) that lead to endocytosis to swelling of the endosome and cracks in the endosomal membrane.
  • On membrane insertion and formation of inverted micelles

After a cell penetration occurred without endocytosis at 4 ° C, a direct, as well as endocytosis and ATP - independent penetration was suspected, but have also been reported artifacts of fixation and staining. For direct penetration, the fact that CPP can also distribute through ER membranes or artificial lipid bilayers. The formation of a membrane pore in the endosomal membrane or the cell membrane was verified experimentally. However speaks for endocytosis unequal distribution of the CPP in different cell compartments, a reduction in the distribution of the CPPs penetratin addition of Endozytosehemmern, a microscopic Kolokalistion with caveolin and a recording via pinocytosis. May be more than one pick-up mechanism runs parallel, in particular the proportions of these mechanisms change with change in the size of the attached molecule or particle. The third mechanism believed the formation of an inverted micelle, in which the phosphate groups of the membrane lipids by the CPP and the aliphatic portions are oriented outwards. Characterized the peptide remains in a hydrophilic environment.

Contrast medium Heparan sulfate Adenosine triphosphate Microscope Royal Society of Chemistry Digital Object Identifier Current Medicinal Chemistry Proceedings of the National Academy of Sciences of the United States of America Pharmaceutical Research (journal) Cell (journal)
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