| RRC ID |
39301
|
| 著者 |
Niidome T, Takaji K, Urakawa M, Ohmori N, Wada A, Hirayama T, Aoyagi H.
|
| タイトル |
Chain length of cationic alpha-helical peptide sufficient for gene delivery into cells.
|
| ジャーナル |
Bioconjug Chem
|
| Abstract |
To define the minimal peptide length needed for gene delivery into mammalian cells, we synthesized several peptides with shortened chain lengths from the amino-termini of the original amphiphilic peptides (4(6), Ac-LARL-LARL-LARL-LRAL-LRAL-LRAL-NH( 2,) and Hel 11-7, KLLK-LLLK-LWKK-LLKL-LK), which have been known to have gene transfer abilities into cells. Each synthetic peptide was studied for its ability to bind and aggregate with plasmid DNA and the structural change of the peptide caused by binding with the DNA to establish a relative in vitro gene transfection efficiency in COS-7 cells. As a result, the deletion of eight amino acid residues of 4(6) had little influence on their ability, whereas that of 12 amino acid residues remarkably reduced the abilities to make aggregates and transfer the DNA into the cell. In the case of the Hel 11-7 series peptides, deletion of amino acid residues caused a considerable reduction in abilities to bind and form aggregates with DNA and to transfer the DNA into cell in due order. In summary, 16 and 17 amino acid residues were sufficient to form aggregates with the DNA and transfer the DNA into the cells in the deletion series of 4(6) and Hel 11-7, respectively. Furthermore, it was indicated that reduction of membrane perturbation activity of the peptide-DNA complex due to deletion of the peptide chain length caused suppression of the transfection efficiency even if the complex was incorporated into the cells. Transfer of the complex to cytosol mediated by membrane perturbation activity of the peptide is an important step for efficient protein expression from its cDNA. The results of this study will make it easy to design and synthesize a functional gene carrier molecule such as a carbohydrate-modified peptide used in targeted gene delivery.
|
| 巻・号 |
10(5)
|
| ページ |
773-80
|
| 公開日 |
1999-1-1
|
| DOI |
10.1021/bc990012d
|
| PII |
bc990012d
|
| PMID |
10502342
|
| MeSH |
Amino Acid Sequence
Animals
CHO Cells
COS Cells
Cations
Cell Membrane / metabolism
Circular Dichroism
Cricetinae
DNA / administration & dosage*
DNA / chemistry
DNA / metabolism
Gene Transfer Techniques*
HeLa Cells
Humans
Molecular Sequence Data
Particle Size
Peptides / administration & dosage*
Peptides / chemical synthesis
Peptides / chemistry*
Peptides / metabolism
Plasmids / genetics
Protein Structure, Secondary
Structure-Activity Relationship
Tumor Cells, Cultured
|
| IF |
4.031
|
| 引用数 |
41
|
|
WOS 分野
|
CHEMISTRY, ORGANIC
CHEMISTRY, MULTIDISCIPLINARY
BIOCHEMICAL RESEARCH METHODS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa S3 (SC)(RCB0271)
CHO-K1(RCB0285)
COS-7(RCB0539) |
