title: A novel 11-residual peptaibol-derived carrier peptide for in vitro oligodeoxynucleotide delivery into cell.
abstract: Using a pore- and channel-forming peptide, TV-XIIa, which is an 11-residual peptaibol isolated from the fungus Trichoderma viride, we developed a vehicle for the cellular delivery of such polar biologically active agents as antisense oligodeoxynucleotides (ODNs). To function as an ODN carrier, basic amino acids, 10-mer of lysine, were conjugated to the C-terminus of TV-XIIa and the designed carrier peptide, Ac-U-N-I-I-U-P-L-L-U-P-I-K-K-K-K-K-K-K-K-K-K-OH (U: alpha-aminoisobutyric acid), was synthesized by the Fmoc-based solid-phase method. The complex between the carrier peptide and ODNs, which was electrostatically formed, was capable of crossing the membranes of NIH3T3 cells and the ODNs were accumulated in the cytoplasm and the nucleus. However, the complex was not taken up by A549 cells. The translocation of the complex occurred at both 4 and 37 degrees C in NIH3T3 cells and did not seem to involve an energy-dependent endocytic process.
authors.affiliation: Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. wadagly.oups.ac.jp
authors.forename: Shun-ich
authors.initials: SI
authors.lastname: Wada
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D054848:Peptaibols; D010455:Peptides / Q000493:pharmacokinetics*; D014242:Trichoderma / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D009838:Oligodeoxyribonucleotides; D054848:Peptaibols; D010455:Peptides; C116937:peptaibolin