Molecular design and synthesis of artificial ion channels based on cyclic peptides containing unnatural amino acids.
Molecular design and synthesis of artificial ion channels based on cyclic peptides containing unnatural amino acids.
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基于含有非天然氨基酸的环肽的人工离子通道的分子设计与合成。
DOI：
10.1002/chin.200134202
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Y. Inoue
中科院分区：
文献类型：
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作者：
H. Ishida;Z. Qi;M. Sokabe;K. Donowaki;Y. Inoue
以长链烷酰基链5-(N-烷酰氨基)-3-氨基苯甲酸为非天然氨基酸，设计合成了一系列由3至5个天然-非天然氨基酸单元交替组成的二肽单元组成的新型环肽。发现所有具有系统变化的孔径、形状和亲脂性的环肽形成电导约为的离子通道。通过电压钳法检查，KCl 水溶液 (500 mM) 中为 9 pS。这些肽通道具有阳离子选择性，渗透率比 P(Cl(-))/P(K(+)) 约为 0.17。分别由含有L-丙氨酸、L-赖氨酸和L-天冬氨酸的中性环肽、阳离子环肽和阴离子环肽形成的离子通道显示出单价阳离子选择性，通透性比值P(Na(+))/P(K(+))约为1。 0.39。根据Ca(2+)对所有测试肽的单通道电流的电压依赖性阻断所提供的结构信息，我们推断每个通道是由肽的二聚体形成的，其肽环构成通道入口，其烷酰基链排列在膜上以构建通道孔。实验结果与离子传导速率由所有通道共有的疏水烷酰基链区域的性质决定的观点相一致。
A series of novel cyclic peptides composed of 3 to 5 dipeptide units with alternating natural-unnatural amino acid units, have been designed and synthesized, employing 5-(N-alkanoylamino)-3-aminobenzoic acid with a long alkanoyl chain as the unnatural amino acid. All cyclic peptides with systematically varying pore size, shape, and lipophilicity are found to form ion channels with a conductance of ca. 9 pS in aqueous KCl (500 mM) upon examination by the voltage clamp method. These peptide channels are cation selective with the permeability ratio P(Cl(-))/P(K(+)) of around 0.17. The ion channels formed by the neutral, cationic, and anionic cyclic peptides containing L-alanine, L-lysine, and L-aspartate, respectively, show the monovalent cation selectivity with the permeability ratio P(Na(+))/P(K(+)) of ca. 0.39. On the basis of structural information provided by voltage-dependent blockade of the single channel current of all the tested peptides by Ca(2+), we inferred that each channel is formed from a dimer of the peptide with its peptide ring constructing the channel entrance and its alkanoyl chains lining across the membrane to build up the channel pore. The experimental results are consistent with an idea that the rate of ion conduction is determined by the nature of the hydrophobic alkanoyl chain region, which is common to all the channels.