A functionalized 20-residue peptaibol derivative for nucleic acid delivery.

Abstract

Based on the membrane-modifying peptaibol trichocellin-A-I (1) from Trichoderma viride, we designed a vehicle for the cellular delivery of antisense oligodeoxynucleotides by attaching a (Lys)10 stretch to the C-terminus of 1. The resulting transporter peptide 2, prepared by solid-phase synthesis using Fmoc protocol in combination with amino acid fluorides, was found to be mainly alpha-helical in solution, in contrast to its precursors 1 and 3. The uptake of the complex formed between carrier 2 and a fluorescence-tagged oligonucleotide, i.e., 4, was studied at different charge ratios by confocal laser-scanning microscopy, using two different eukaryotic cell lines: mouse embryonal fibroblast (NIH3T3) and human lung carcinoma (A549) cells. Peptide 2 readily translocated 4 into the cytoplasms of NIH3T3 cells. However, the peptide/oligonucleotide complex was accumulated around the plasma membrane of the A549 cells.

• Authors: Shun-ichi Wada, Reiko Tanaka
• Journal: Chemistry & biodiversity (Chem Biodivers) Vol. 4 Issue 5 Pg. 991-7 (May 2007) ISSN: 1612-1880 [Electronic] Switzerland
• PMID: 17510994 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• Nucleic Acids
• Peptaibols
• Peptides
• trichocellin

Topics

• 3T3 Cells
• Animals
• Biological Transport (physiology)
• Cell Proliferation (drug effects)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Fibroblasts (metabolism)
• Humans
• Mice
• Nucleic Acids (administration & dosage)
• Peptaibols
• Peptides (chemistry)
• Tumor Cells, Cultured