Construction of novel 2-screw helices of polypeptides designed with a concept of dipeptide mimics

折叠体是通过非共价相互作用折叠成构象有序状态的任何功能性低聚物。天然多肽具有3倍或以上的螺旋结构（α-螺旋或3_<10>-螺旋），而不具有2倍螺旋结构。在本研究中，我们主要基于二肽模拟的概念来研究2-氨基苯氧乙酸。我们发现2-氨基苯氧乙酸低聚物通过分子内氢键形成2重螺旋结构。这些拟肽折叠体将为生物化学和肽化学领域提供一类新的人工肽。我们合成了2-硝基苯氧乙酸和2-氨基苯氧乙酸衍生物，并将这些成分偶联得到二聚体到四聚体。新型螺旋折叠体的结构和性质：(1)这些低聚物的诱导螺旋度随着手性单元的增加而增强。单晶x射线分析显示，该四聚体在固体状态下具有2重螺旋结构。(2)在环己烷中，四聚体中只有一个c端手性碳引起了强烈的CD谱棉花效应，表明其全链呈螺旋状。(3)极性溶剂削弱了分子内氢键，降低了折叠物的诱导CD光谱。然而，在所有α-碳上带有甲基的折叠体几乎不受溶剂效应的影响，因为它们的折叠是由α-甲基的空间效应引起的。为了快速高效地制备低聚物，通常采用固相法合成9-氟甲氨基甲酸酯（FMOC）制备这些低聚物。分子间相互作用对折叠膜结构的控制：合成了两个苯环上各含羧基的折叠膜。功能化低聚物上的两个羧基与手性二胺立体选择性相互作用。低聚物与（S，S）-环己二胺的盐形成稳定了极性溶剂中的螺旋结构。因此，我们通过分子间相互作用来控制低聚物的折叠。

A foldamer is any functional oligomer that folds into a conformationally ordered state by noncovalent interactions. Natural polypeptides have 3-fold or above helices (α-helix or 3_<10>-helix), but no 2-fold helix. In this research, we focus on the 2-aminophenoxyacetic acids based on the concept of dipeptide mimicking. We found the 2-aminophenoxyacetic acid oligomer construct 2-fold helix by intramolecular hydrogen bonding. These peptidomimetic foldamers will provide a new class of artificial peptides in biochemistry and peptide chemistry.1.We synthesized 2-nitrophenoxyacetic acid and 2-aminophenoxyacetic acid derivatives and coupled these components to obtain from the dimer to the tetramer.2.Structure and properties of the novel helix as a foldamer : (1)Induced helicity of these oligomers becomes stronger with increasing chiral units. Single-crystal X-ray analysis of the tetramer revealed 2-fold helical structure in solid state. (2)In cyclohexane, only one C-termial chiral carbon of the tetramer induced strong Cotton effect of the CD spectrum, which suggested the helicity on its whole chain. (3)Polar solvents weaken intramolecular hydrogen bonds to reduce induced CD spectra of the foldamers. However foldamers bearing methyl groups on all α-carbons are almost independent of solvent effects because of folding by steric effects of their α-methyl groups.3.For the sake of rapid and efficient preparation of oligomers, usual solid phase syntheses of 9-fluorenylmethylcarbamate (FMOC) method was applicable to these foldamers.4.Structural control of foldamers by intermolecular interactions : The foldamer bearing each carboxyl group of their two benzene rings was synthesized. Two carboxyl groups on the functionalized oligomer interacted with a chiral diamine stereoselectively. Salt forming of the oligomer with (S,S)-cyclohexanediamine stabilized the helical structure in polar solvent. Thus we controlled the folding of the oligomer by intermolecular interactions.