Transduction domain

The antiparallel strand structure between residues 131 and 238 in the cytoplasmic portion of Ca -ATPase was originally designated as transduction domain the name suggested its possible role in the conformational coupling between the nucleotide binding and phosphorylation sites exposed to the cytoplasm and the Ca channel located at some distance from each other in the lipid bilayer [8,42]. The site specific mutagenesis of conserved amino acids in the P strand sector of the molecule provides support for its proposed function in conformational transitions [103,126,127,215]. 

Console S, et al. Antennapedia and HIV transactivator of transcription (TAT) protein transduction domains promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans. J Biol Chem 2003 278 35109. 

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. 

Cao G, Pei W, Ge H, et al. In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. J Neurosci 2002 22(13) 5423-5431. 

Park J, Ryu J, Kim KA, et al. Mutational analysis of a human immunodeficiency virus type 1 Tat protein transduction domain which is required for delivery of an exogenous protein into mammalian cells. J Gen Virol 2002 83(Pt 5) 1173-1181. 

Lundberg M, Wikstrom S, Johansson M. Cell surface adherence and endocyto-sis of protein transduction domains. Mol Ther 2003 8(1) 143-150. 

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. 

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

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). 

Polypyrimidine tract-binding protein, a repressive regulator of protein splicing also pulmonary tuberculosis Protein transduction domain... 

Eguchi, A., Akuta, T., Okuyama, H., et al. (2001) Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of DNA into mammalian cells. J. Biol. Chem. 276, 26,204-26,210. 

Green I, Christison R, Voyce CJ, Bundell KR, Eindsay MA. Protein transduction domains Are they delivering Trends Pharmacol Sci 2003 24 213-5. 

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. 

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