A Functionalized 20-Residue Peptaibol Derivative for Nucleic Acid Delivery
✍ Scribed by Shun-ichi Wada; Reiko Tanaka
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 189 KB
- Volume
- 4
- Category
- Article
- ISSN
- 1612-1872
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✦ Synopsis
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 α‐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.