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

折叠体是任何通过非共价相互作用折叠成构象有序状态的功能性低聚物。天然多肽具有3倍或3倍以上的螺旋(α-螺旋或3&lt；10-螺旋)，但没有2倍螺旋。在这项研究中，我们重点研究了基于二肽类概念的2-氨基苯氧基乙酸。我们发现2-氨基苯氧基乙酸齐聚物通过分子内氢键形成2重螺旋。1.我们合成了2-硝基苯氧基乙酸和2-氨基苯氧基乙酸的衍生物，并将这些组分从二聚体偶联为四聚体。2.新型螺旋作为折叠剂的结构和性质：(1)这些寡聚体的诱导螺旋性随手性单元的增加而增强。对四聚体进行了单晶X-射线分析，结果表明该四聚体在固态下具有2重螺旋结构。(2)在环己烷中，只有一个四聚体的C端手性碳诱导了CD光谱的强烈的Cotton效应，这表明它的全链是螺旋性的。(3)极性溶剂削弱了分子内氢键，降低了诱导环糊精谱。3.为了快速高效地制备低聚物，常用的固相合成方法9-荧甲基氨基甲酸酯(Fmoc)适用于这些低聚物的制备。4.通过分子间相互作用对低聚物进行结构控制：合成了含两个苯环上的每个羧基的α-α。官能化齐聚物上的两个羧基与手性二胺发生立体选择性相互作用。低聚物与(S，S)-环己二胺成盐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.