Ishida Hitoshi, Kyakuno Masato, Oishi Shigero
Department of Chemistry, School of Science, Kitasato University, Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Biopolymers. 2004;76(1):69-82. doi: 10.1002/bip.10581.
Unnatural amino acids are effective as building blocks to design functional peptides from the following two points: (1) utilization of rigid unnatural amino acids for the incorporated peptides to control the conformation to appear the function, and (2) incorporation of functional and unnatural amino acids into peptides resulting in appearance of the inherent functions. As a combined strategy, molecular design of artificial metalloproteins utilizing 5'-amino-2,2'-bipyridine-5-carboxilic acid (H-5Bpy-OH) as an unnatural amino acid is proposed. The peptide containing three residues of the unnatural amino acid would fold through coordination to a metal ion. In particular, ruthenium(II) ion would yield a ruthenium tris(bipyridine) derivative as the core complex of the artificial protein, which would appear the similar photochemical functions as that of ruthenium(II) tris(bipyridine) complex. The central complex could form two isomers, fac and mer. For selective synthesis of the mer complex, which is expected as the core complex in the artificial protein, dicyclohexylamide as a bulky group is introduced at the C-terminal of the unnatural amino acid to destabilize the fac complex due to steric hindrance. Furthermore, in order to know the photochemical properties and function of the protein mimics, ruthenium(II) tris(2,2'-bipyridine) complexes bearing amide groups at 5,5' positions have been synthesized as the model complexes. As a result, the direction of amide groups (RNHCO-or RCONH-) in ruthenium complexes is found to significantly affect the emission efficiency: the former reduces the quantum yield and the latter enhances it, respectively. The ruthenium(II) tris(5,5'-diamide-2,2'-bipyridine) complexes are also found to strongly bind with various anions [e.g., halogen ions (Cl-, Br-) and acetate anion] in acetonitrile and to detect these anions through the emission spectral changes under air. The molecular design of artificial protein is expected to develop new fields among peptide, organic, inorganic, and physical chemistry.
非天然氨基酸作为构建功能肽的有效组成部分，基于以下两点：（1）利用刚性非天然氨基酸来控制所嵌入肽的构象以展现其功能；（2）将功能性非天然氨基酸嵌入肽中从而使固有功能得以显现。作为一种组合策略，提出了利用5'-氨基-2,2'-联吡啶-5-羧酸（H-5Bpy-OH）作为非天然氨基酸来进行人工金属蛋白的分子设计。含有三个非天然氨基酸残基的肽将通过与金属离子配位而折叠。特别地，钌（II）离子会生成作为人工蛋白核心配合物的三（联吡啶）钌衍生物，其将展现出与三（联吡啶）钌（II）配合物相似的光化学功能。中心配合物可以形成两种异构体，面式和经式。为了选择性合成预期作为人工蛋白核心配合物的经式配合物，在非天然氨基酸的C端引入二环己基胺作为大位阻基团，由于空间位阻使面式配合物不稳定。此外，为了了解蛋白质模拟物的光化学性质和功能，已合成了在5,5'位带有酰胺基团的三（2,2'-联吡啶）钌（II）配合物作为模型配合物。结果发现，钌配合物中酰胺基团的方向（RNHCO-或RCONH-）对发射效率有显著影响：前者降低量子产率，后者提高量子产率。还发现三（5,5'-二酰胺-2,2'-联吡啶）钌（II）配合物在乙腈中能与各种阴离子[如卤素离子（Cl-，Br-）和醋酸根阴离子]强烈结合，并在空气中通过发射光谱变化检测这些阴离子。人工蛋白的分子设计有望在肽化学、有机化学、无机化学和物理化学等领域开拓新的方向。
