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

以二肽模拟物概念设计的新型多肽双螺旋结构的构建

基本信息

批准号：
16550120
负责人：
AKAZOME Motohiro
金额：
$ 1.98万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

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.

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寡聚体。天然多肽具有3倍或以上螺旋（α-螺旋或3_<10>-螺旋），但没有2倍螺旋。本论文基于二肽模拟的概念，对2-氨基苯氧乙酸类化合物进行了研究。我们发现2-氨基苯氧乙酸寡聚体通过分子内氢键形成2重螺旋结构。1.合成了2-硝基苯氧乙酸和2-氨基苯氧乙酸的衍生物，并将其偶联得到二聚体和四聚体。2.新型螺旋折叠体的结构和性质：（1）这些低聚体的诱导螺旋性随着手性单元的增加而增强。四聚体的单晶X-射线分析显示在固态下具有2倍螺旋结构。(2)In环己烧，四聚体中只有一个C端手性碳引起CD光谱的强烈Cotton效应，这表明其整个链上具有螺旋性。（3）极性溶剂削弱了分子内的氢键，降低了折叠体的诱导CD谱。然而，由于α-甲基的空间位阻效应，所有α-碳上都带有甲基的折叠体几乎不受溶剂的影响。3.为了快速有效地制备低聚物，通常的固相合成9-芴基甲基氨基甲酸酯（FMOC）方法适用于这些折叠体。4.通过分子间相互作用控制折叠体的结构：合成了两个苯环上均带有羧基的折叠体。官能化低聚物上的两个羧基与手性二胺立体选择性地相互作用。在极性溶剂中，低聚物与（S，S）-环己二胺成盐稳定了螺旋结构。因此，我们通过分子间的相互作用来控制寡聚体的折叠。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Separeation and Reactions in Organic Supramolecular Chemistry

有机超分子化学中的分离与反应

DOI：
发表时间：
2004
期刊：
影响因子：
0
作者：
Motohiro Akazome;Kenichi Ogu;Kenichi Ogu;Motohiro Akazome;Motohiro Akazome;Katsuyuki Ogura;Katsuyuki ogura
通讯作者：
Katsuyuki ogura

Novel Synthesis of α-Trifluoromethylated α-Amino Acid Derivatives from γ-Hydroxy-α-fluoro-α-trifuluoromethyl Carboxamides

由γ-羟基-α-氟-α-三氟甲基甲酰胺新合成α-三氟甲基化α-氨基酸衍生物