Required structure of cationic peptide for oligonucleotide-binding and -delivering into cells

Improvement of the methods for oligonucleotide: delivery into cells is nece ssary for the development of antisense therapy. In the present work, a new strategy for oligonucleotide delivery into cells was tested using cationic peptides as a vector. At first, to understand what structure of the peptide is required for binding with an oligonucleotide, several kinds of alpha-he lical and non-alpha-helical peptides containing cationic amino acids were e mployed. As a result, the amphiphilic: alpha-helix peptides were best for b inding with the oligonucleotide, and the long chain length and large hydrop hobic region in the amphiphilic structure of the peptide were necessary for the binding and forming of aggregates with the oligonucleotide. In the cas e of non-alpha-helical peptides, no significant binding ability was observe d even if their chain lengths and number of cationic amino acid residues we re equal to those of the alpha-helical peptides. The remarkable ability of oligonucleotide delivery into COS-7 cells was observed in the alpha-helical peptides with a long chain length and large hydrophobic region in the amph iphilic structure, but was not observed in the non-alpha-helical peptides. It is considered that such cc-helical peptides could form optimum aggregate s with the ODN for uptake into cells. Based on these results, the alpha-hel ical peptide with a long chain length and large hydrophobic region is appli cable as a vector for the delivery of oligonucleotides into cells. Copyrigh t (C) 2000 European Peptide Society and John Wiley gr Sons, Ltd.