Peptide transduction domains

Meade BR, Dowdy SF (2007) Exogenous siRNA delivery using peptide transduction domains/cell penetrating peptides. Adv Drug Deliv Rev 59 134-140... 

Kaplan IM, Wadia IS, Dowdy SF. Cationic TAT peptide transduction domain enters cells by macropinocytosis. J Control Release 2005 102 247-253. 

Tkachenko AG, Xie H, Liu YL, Coleman D, Ryan J, Glomm WR, et al. Cellular trajectories of peptide-modified gold particle complexes comparison of nuclear localization signals and peptide transduction domains. Bioconjug Chem 2004 15 482-90. 

Snyder, E. L. and S. F. Dowdy, 2001, Protein/peptide transduction domains potential to deliver large DNA molecules into cells. Curr Opin Mol Ther 3 147-152. 

Alberts, B., et al.. Molecular Biology of the Cell. 1994, New York Garland Publishing, Inc. 1294. Tkachenko, A.G., et al.. Cellular Trajectories of Peptide-Modified Gold Particle Complexes Comparison of Nuclear Localization Signals and Peptide Transduction Domains. Bioconjugate Chem., (2004). 15 p. 482-490. 

Eguchi A, Meade BR, Chang YC, Fredrickson CT, Willert K, Puri N, Dowdy SF (2009) Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein. Nat Biotechnol 27 567-571... 

An example of this class of peptide is the 86-amino acid truKi-activating transcriptional activator (TAT) of HIV-1 (74,75). Following incubation with cultured cells, TAT protein is internalized and subsequently transactivates viral promoters (75). The protein has multiple facets invasion, nuclear trophism, and DNA binding (76-81). An invasion domain of TAT has been identified within amino acids 37 to 72 with the critical basic region from amino acids (49 to 57), also known as the minimal transduction domain, which consists of the sequence -Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-. Any deletion in the sequence caused a reduction in translocating activity (82-84). Other prominent CPPs are reviewed in References 73 and 85. 

Hyndman L, Lemoine JL, Huang L, et al. HIV-1 Tat protein transduction domain peptide facilitates gene transfer in combination with cationic liposomes. J Control Release 2004 99(3) 435 44. 

Already in 1965, Ryser and Hancock provided evidence that histones and polyamino acids could greatly enhance albumin uptake by cultured tumor cells (6). More recently, several polybasic peptides (so-called protein transduction domains, PTDs or cell-penetrating peptides, CPPs) have been shown to efficiently mediate uptake of nucleic acids, bioactive peptides, phage particles, and liposomes into a wide variety of mammalian cells. The initially proposed ability of CPPs to penetrate plasma membranes via a temperature-independent, non-endocytotic pathway was later shown to be a fixation artifact, and it is currently widely accepted that CPP-mediated macromolecular delivery follows energy-dependent endocytotic pathways that in most cases depend on the expression of cell-surface heparan sulfate proteoglycans (HSPGs) (7). 

A peptide (DPI), comprised of a protein transduction domain fused to an antimicrobial peptide (AMP) KLAKLAKKLAKLAK, triggered apoptosis in murine fibrosarcoma (MCA205) and human head and neck tumor cell lines in vitro. It also induced tumor apoptosis and reduction of tumor volume (MCA205) by direct intratumor injection [245]. 

Becker et al. [64] functionalized a peptide, based on the protein transduction domain of the HIV protein TAT-1, with an NMP initiator while on the resin. They then used this to polymerize f-butyl acrylate, followed by methyl acrylate, to create a peptide-functionahzed block copolymer. Traditional characterization of this triblock copolymer by gel permeation chromatography and MALDI-TOF mass spectroscopy was, however, comphcated partly due to solubility problems. Therefore, characterization of this block copolymer was mainly hmited to ll and F NMR and no conclusive evidence on molecular weight distribution and homopolymer contaminants was obtained. Difficulties in control over polymer properties are to be expected, since polymerization off a microgel particle leads to a high concentration of reactive chains and a diffusion-limited access of the deactivator species. The traditional level of control of nitroxide-mediated radical polymerization, or any other type of controlled radical polymerization, will therefore not be straightforward to achieve. 

Cell-penetrating peptides (CPPs), Trojan horse peptides, protein transduction domains, peptides of different stmctural classes that are capable to cross the plasma membranes of mammalian cells in an... 

Over the past decade, the unique activity of oligopeptides, known as protein transduction domains (PTDs) or cell penetrating peptides (CPPs), has made it possible to transduce biologically active macromolecules into living cells [2, 3]. It was accomplished by conjugating a PTD to the desired macromolecule. Various kinds of macromolecules have been successfully internalized into living... 

The cell-penetrating peptides (CPPs), also called protein transduction domains, were discovered in 1988 almost simultaneously by two research teams. However, interest in CPPs began only in 1994, when it was found that the HIV-l-trans-activating protein (Tat protein) can be covalently attached to very different cargoes, such as low molecular weight compounds, peptides, " " proteins, polysaccharides, oligonucleotides, " nucleic... 

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