Importance of hydrophobic region in amphiphilic structures of alpha-helical peptides for their gene transfer-ability into cells.

Importance of hydrophobic region in amphiphilic structures of alpha-helical peptides for their gene transfer-ability into cells.
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α-螺旋肽的两亲结构中的疏水区域对于其基因转移到细胞中的能力的重要性。

DOI:
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发表时间:
1998
期刊:
Biochemical and Biophysical Research Communications - BBRC
影响因子:
--
通讯作者:
H. Aoyagi
H. Aoyagi
中科院分区:
--
文献类型:
--
作者:
N. Ohmori;T. Niidome;T. Kiyota;S. Lee;G. Sugihara;A. Wada;T. Hirayama;H. Aoyagi

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已显示阳离子α-螺旋肽可用作核酸载体分子,用于将基因转移到细胞中。为了探讨两亲性肽中疏水区对转染能力的重要性,我们选用了5种疏水-亲水平衡系统变化的两亲性肽,并评价了两亲性肽的结构与其转染COS-7细胞的能力之间的关系。具有大的疏水区域的肽呈α-螺旋结构,形成大的聚集体,并显示出高的转染效率。它们的高效率可以根据它们形成稳定的聚集体的能力来解释,所述聚集体可以通过内吞作用内化并且保持对溶酶体囊泡中的消化的抗性。此外,还表明肽的疏水区在破坏内体膜中起重要作用,其可阻止溶酶体囊泡中的DNA降解。当肽不具有如此强的膜破坏活性,但形成可通过内吞作用掺入的聚集体时,转染效率可通过加入内体破坏肽来恢复。
It has been showned that cationic alpha-helical peptides can be useful as nucleic acid-carrier molecules for gene transfer into cells. In order to investigate the significancemake sure of importance of the hydrophobic region in amphiphilic peptides in relation to their transfection ability, we have employed five kinds of peptides with a systematically varied hydrophobic-hydrophilic balance in the amphiphilic structures, and have evaluated the relationship between the structure and the gene transfer ability of the peptides into COS-7 cells. The peptides with a large hydrophobic region took alpha-helical structures, formed large aggregates and showed high transfection efficiency. Their high efficiency can be explained on the basis of their ability to form stable aggregates which can be internalized by endocytosis and remain resistant to digestion in lysosomal vesicles. Furthermore, it was suggested that the hydrophobic region of peptides plays an important role in the disruption of the endosomal membrane, which ca prevent the degradation of DNA in lysosomal vesicles. When peptides do not have so strong membrane-disruptive activity, but form aggregates which can be incorporated by endocytosis, the transfection efficiency can be recovered by the addition of an endosome-disruptive peptide.
DOI: 10.1021/bi9618474
发表时间: 1997-03-11
期刊: BIOCHEMISTRY
影响因子: 2.9
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期刊: BIOCHEMISTRY
影响因子: 2.9
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PARENTE, RA;NADASDI, L;SZOKA, FC
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