| RRC ID |
39450
|
| 著者 |
Niidome T, Urakawa M, Takaji K, Matsuo Y, Ohmori N, Wada A, Hirayama T, Aoyagi H.
|
| タイトル |
Influence of lipophilic groups in cationic alpha-helical peptides on their abilities to bind with DNA and deliver genes into cells.
|
| ジャーナル |
J Pept Res
|
| Abstract |
For the purpose of achieving gene transfer into cells mediated by peptides with a short chain length, we employed two kinds of amphiphilic alpha-helix peptides, mastoparan (INLK-ALAA-LAKK-IL-NH2) obtained from wasp venom and an alpha-helix model peptide (LARL-LARL-LARL-NH2). Furthermore, to strengthen the hydrophobicity of the peptide required for the formation of the aggregates with the DNA, we modified these peptides using several lipophilic groups, i.e. acyl groups with a single chain, a dialkylcarbamoyl group and a cholesteryloxycarbonyl group. We examined the ability of the peptides and their derivatives to bind and aggregate with plasmid DNA, the structural change in the peptides caused by binding with the DNA and the in vitro gene transfer abilities into COS-7 cells. As a result, mastoparan was found to acquire the DNA binding ability by introduction of the lipophilic group. The conformational change in the peptides depended on the hydrophobicity of the introduced acyl group. The DNA complex of most lipophilic mastoparan derivatives could be incorporated into the cells via the endocytosis pathway. In the case of the helix model peptide, the acyl group with a moderate chain length was required for the formation of the aggregate which is competent for incorporation into the cells. In this study, we succeeded in giving such short peptides sufficient gene transfer ability by modifying them with some lipophilic groups. However, the influence of the modification by the lipophilic groups on the formation of aggregates with DNA and the gene transfer ability depended on the structure of the peptide portion. These results indicate that consideration of total hydrophobicity balance is needed for the design of an efficient gene carrier peptide.
|
| 巻・号 |
54(4)
|
| ページ |
361-7
|
| 公開日 |
1999-10-1
|
| DOI |
10.1034/j.1399-3011.1999.00122.x
|
| PII |
122
|
| PMID |
10532242
|
| MeSH |
Amino Acid Sequence
Cell Line
DNA / metabolism*
Gene Transfer Techniques*
Intercellular Signaling Peptides and Proteins
Lipid Metabolism
Molecular Sequence Data
Peptide Biosynthesis
Peptides / chemistry
Peptides / metabolism*
Protein Conformation
Wasp Venoms / chemistry
Wasp Venoms / metabolism
|
| 引用数 |
33
|
|
WOS 分野
|
BIOCHEMICAL RESEARCH METHODS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
