Transduction peptides: from technology to physiology

  title={Transduction peptides: from technology to physiology},
  author={Alain Joliot and Alain Prochiantz},
  journal={Nature Cell Biology},
During the past fifteen years, a variety of peptides have been characterized for their ability to translocate into live cells. Most are efficient vectors that can internalize hydrophilic cargoes, and so provide a valuable biological (and potentially therapeutic) tool for targeting proteins into cells. Furthermore, translocation of cell-permeable peptides across the plasma membrane and their subsequent access to the cytosol, even when fused to large hydrophilic proteins, is challenging the… 

Protein transduction technology: a novel therapeutic perspective.

The main mechanism of protein transduction is an electrostatic interaction with the plasma membrane, penetration into cells by macropinocytosis, and a release to cytoplasm and nuclei by retrograde transport.

Recent Advances in Protein Transduction Technology

The use of the NH2-terminal domain of the influenza virus hemagglutinin-2 subunit (HA2) or photosensitive PTDs has been shown to specifically enhance macropinosome escape and create a number of possibilities for the development of new peptide-based drugs.

Development and Application of Cell-penetrating Peptides

The history and characteristics of CPPs are introduced and the intracellular transduction mechanism and application are focused on, including cell penetrating peptide.

Recent advances in the use of protein transduction domains for the delivery of peptides, proteins and nucleic acids invivo

Evidence that PTDs can be used both to deliver active molecules to pathological tissue invivo and to treat models of disease such as cancer, ischaemia and inflammation is reviewed.

Influence of protein transduction domains on intracellular delivery of macromolecules

The implications of peptide/protein transduction domain-mediated delivery of macromolecules and their possible uses as important primary drug delivery agents are discussed.

Cell-penetrating peptides: small from inception to application

A brief history of the field is given, followed by an introduction to some of the better known and more widely used CPPs, including some of their current applications, and a discussion of the translocation mechanism(s) and the controversies surrounding it.

Homeoprotein intercellular transfer, the hidden face of cell-penetrating peptides.

Some of these functions of CPPs are described and it is proposed that this class of signaling molecules, in particular homeoproteins, may also be used as therapeutic agents.

Cell-Penetrating Peptides: A Challenge for Drug Delivery

An overview of the current approaches and the potential of CPP-based drug delivery systems are described and their powerful promise for clinical efficacy is indicated.

Peptide-Mediated Membrane Transport of Macromolecular Cargo Driven by Membrane Asymmetry.

It is found that β-galactosidase translocation is driven only by the negative transmembrane potential resulting from the asymmetric bilayers, which may be generally applicable for high-throughput screening of the efficacy of cell-penetrating peptides.



A peptide carrier for the delivery of biologically active proteins into mammalian cells

A new strategy for protein delivery based on a short amphipathic peptide carrier, Pep-1, which is able to efficiently deliver a variety of peptides and proteins into several cell lines in a fully biologically active form, without the need for prior chemical covalent coupling or denaturation steps.

In vivo protein transduction: delivery of a biologically active protein into the mouse.

It is shown that intraperitoneal injection of the 120-kilodalton beta-galactosidase protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain.

Tilted peptides: a motif for membrane destabilization (Hypothesis)

This hypothesis overviews the discovery of tilted peptides, describes how they are detected and discusses how they could be involved in dynamic biological processes.

Messenger proteins: homeoproteins, TAT and others.

Cell membrane translocation of the N-terminal (1-28) part of the prion protein.

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters.

Overall, a transporter has been developed that is superior to Tat(49-57), protease resistant, and more readily and economically prepared and suggest that the guanidinium groups of Tat( 49-57) play a greater role in facilitating cellular uptake than either charge or backbone structure.

Peptides fused to the amino-terminal end of diphtheria toxin are translocated to the cytosol

The results are compatible with a model in which the COOH-terminus of the A-fragment first crosses the membrane, whereas the NH2-terminal region follows behind, and neither hydrophobic nor highly charged sequences blocked translocation.