Molecular design and synthesis of artificial ion channels based on cyclic peptides containing unnatural amino acids

被引:63
作者
Ishida, H
Qi, Z
Sokabe, M
Donowaki, K
Inoue, Y
机构
[1] ERATO, Japan Sci & Technol, Inoue Photochirogenesis Project, Toyonaka, Osaka 5600085, Japan
[2] Nagoya Univ, Sch Med, Dept Physiol, Showa Ku, Nagoya, Aichi 4668550, Japan
[3] Japan Sci & Technol, ICORP, Cell Mechanosensing Project, Nagoya, Aichi 4668550, Japan
[4] Osaka Univ, Dept Mol Chem, Suita, Osaka 5650871, Japan
关键词
D O I
10.1021/jo001079t
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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 PCl-/PK+ 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 PNa+,/PK+ 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 Ca2+, 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.
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收藏
页码:2978 / 2989
页数:12
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