蛋白质中蕴含着大自然亿万年的进化智慧，是生物体内各类生理功能的执行者，这些功能的实现取决于其独特的三维结构。天然蛋白质的结构稳定性受到多种因素的影响，比如氨基酸残基的突变或外界环境的扰动就可能影响蛋白质的正确折叠，继而导致蛋白质相关疾病的发生。β-转角和β-发卡作为蛋白质二级结构的重要组成部分，在蛋白质的折叠和一些生物过程中扮演着关键的角色。但是天然的β-转角和β-发卡可能稳定性不佳，在某些情况下易于发生分子间自组装。另外，这些天然寡肽难以实现结构修饰，限制了对它们的进一步研究。对这些二级结构进行仿生，构建人工的β-转角和β-发卡不仅有望扩展制造出新型功能分子，也有益于促进纳米科技、生物医学等前沿学科的发展。本论文利用喹啉和芳香γ-氨基酸单元成功构建了一类人工β-转角，并凭借此人工β-转角诱导寡肽合成得到了人工β-发卡分子。本论文的研究工作主要包括：

1.首先设计合成了四个含有非天然氨基酸单元的分子Turn1~4。其中，Turn1和Turn2的骨架由位于环区的8-氨基-2-喹啉羧酸衍生物和芳香γ-氨基酸共同组成。非天然寡肽分子Turn1和Turn2在分子内氢键的诱导作用下弯折，呈现类似β-转角的构象。因Turn2具有更强的骨架刚性，其转角的稳定性优于Turn1。在分子Turn3和Turn4中，用α-氨基酸替换掉芳香γ-氨基酸单元，分子的折叠倾向则会受到明显削弱，导致人工转角Turn3和Turn4的稳定性下降。结果表明，环区单元和芳香γ-氨基酸的结构均能影响转角模拟物的折叠性质。

2. 在人工β-转角Turn1~2基础上，在分子两端分别接入三肽链，得到人工β-发卡Hairpin1和Hairpin2。经一系列的核磁测试研究发现，人工β-转角可以诱导肽链序列形成β-折叠，从而形成稳定的β-发卡结构。值得一提的是，Hairpin2不仅在有机溶液中能够形成β-发卡结构，而且在重水含量低于40%的环境中，这种有序的β-发卡结构仍然可以稳定存在。

综上，本论文成功构建了一系列稳定性好的β-转角和β-发卡模拟物。这些人工仿生分子在弱极性有机溶剂中能保持折叠。人工发卡Hairpin2甚至能够在含水的媒介中保持其折叠状态，有望进一步开发成为一种人工分子伴侣，挖掘其在缓解或纠正蛋白质的错误折叠等方面的潜在应用。

Proteins embody the evolutionary wisdom of nature over billions of years and are the executors of various physiological functions within living organisms. The realization of these functions depends on their unique three-dimensional structures. The structural stability of natural proteins is influenced by various factors. For example, mutations in amino acid residues or external environmental disturbances may affect the correct folding of proteins, which could potentially lead to the occurrence of protein-related diseases. β-turns and β-hairpins, as important components of protein secondary structures, play a crucial role in protein folding and some biological processes. However, natural β-turns and β-hairpins may not be stable and are prone to undergo intermolecular self-assembly under certain circumstances. In addition, these natural oligopeptides are difficult to conduct structural modification, limiting their further research. Biomimicking these secondary structures and constructing artificial β-turns and β-hairpins not only hold promise for expanding the manufacture of new functional molecules but also benefit the development of cutting-edge disciplines such as nanoscience and biomedicine. In this thesis, we successfully constructed a class of artificial β-turns using quinoline and aromatic γ-amino acid units and induced the synthesis of artificial β-hairpin molecules using these artificial β-turns. The main research work of this thesis includes: 1.First, four molecules (Turn1~4) containing unnatural amino acid units were designed and synthesized. Among them, the building blocks of Turn1 and Turn2 bear 8-amino-2-quinoline carboxylic acid derivatives at the loop region and aromatic γ-amino acids. The non-natural oligopeptide molecules Turn1 and Turn2 adopt a β-turn like conformation that is induced by intramolecular H-bond. The stability of folded Turn2 is stronger than that of Turn1 due to increased backbone rigidity of Turn2. If the aromatic γ-amino acid residues are replaced with α-amino acids, leading to the molecules Turn3 and Turn4, the folding tendency of the corresponding molecules will be significantly weakened, resulting in a decrease in the stability of the artificial turns. The results show that both building blocks play important roles to the folding behavior of the β-turn mimics. 2.Based on the artificial β-turns Turn1~2, tripeptide chains were introduced at the two ends of the molecules, yielding the artificial β-hairpins Hairpin1 and Hairpin2. Through a series of nuclear magnetic resonance studies, it was found that the artificial β-turn can induce the peptide chain sequence to form a β-sheet, thereby forming a stable β-hairpin structure. It is worth mentioning that Hairpin2 can not only form a β-hairpin structure in organic solvents but also maintain this ordered β-hairpin structure when placed in an environment containing deuterium oxide less than 40%. In summary, this thesis successfully have constructed a series of stable β-turn and β-hairpin mimics. These artificial biomimetic molecules can maintain their folded conformation in the low polar organic solvents. Notably, Hairpin2 maintains the folded conformation even in an aqueous environment, showing promise for further potential applications such as artificial molecular chaperone to alleviate or correct protein misfolding.