蛋白质作为一种有机大分子，是生物进行生命活动的功能基础。β-转角作为一种常见的蛋白质二级结构，它们在蛋白质参与的生理活动中扮演着重要的作用，如蛋白-蛋白作用。在天然的蛋白质中，β-转角的结构多样，且稳定性有限，难以对其结构进行直接研究，该领域的研究发展在一定程度上受到了限制。为解决这一问题，构建构象相对稳定的人工β-转角分子具有重要的研究意义。通过开发结构新颖的人工β-转角体系，一方面实现了对天然的β-转角结构进行模拟，探究人工转角体系的构效关系规律，另一方面可以让人们更深入地理解天然β-转角的关键形成因素，有助于诠释它在稳定蛋白质二级结构中发挥的重要作用。
本论文第一章对蛋白质的二级结构进行了简要介绍。其中，针对β-转角模拟物近年来的研究进展进行了梳理和总结。
在本研究中，我们采用两类非天然的氨基酸作为结构单元，构筑了一种β-转角模拟物分子。该分子以γ-氨基酸（5-氨基水杨酸）衍生物作为β-转角模拟物的“C端氨基酸”和“N端氨基酸”。将这两个非天然氨基酸通过酰胺键与一个8-氨基喹啉-2-羧酸片段连接，组成转角模拟物分子。该化合物预期能够通过分子两端5-氨基水杨酸上互补的氢键结合位点，形成分子内氢键，并诱导该分子发生折叠，形成U形回折，从而模拟天然的β-转角结构。
最后，我们通过核磁共振技术，初步研究了目标分子形成β-转角分子模拟物的能力。实验结果发现，该分子的确可以在氢键的驱动下发生折叠，使其呈现类似β-转角的构象。
 

As a kind of organic macromolecule, protein is the functional basis of biological activities. As a common protein secondary structure, β-turn play an important role in the physiological activities involved in proteins, such as protein-protein interaction. In natural proteins, the structure of β-turn is diverse and its stability is limited, so it is difficult to directly study its structure, and the research development in this field is limited to a certain extent. To solve this problem, it is important to construct artificial β-turn molecules with relatively stable conformation. Through the development of artificial β-turn system with novel structure, on the one hand, natural β-turn structure can be simulated and the structure-activity relationship law of artificial β-turn system can be explored. On the other hand, the key formation factors of natural β-turn can be more deeply understood, which is helpful to interpret its important role in the stability of protein secondary structure.
In the first chapter, the secondary structure of proteins is briefly introduced. The research progress of β-turn simulator in recent years is reviewed and summarized.
In this study, we used two unnatural amino acids as structural units to construct a β-turn analog molecule. The molecule uses gamma-amino acid (5-aminosalicylic acid) derivatives as the "C-terminal amino acid" and "N-terminal amino acid" of the β-corner simulation. The two unnatural amino acids were connected with an 8-amino-quinolin-2-carboxylic acid fragment by amide bond to form a corner analog molecule. The compound is expected to be able to form intramolecular hydrogen bonds through complementary hydrogen bond binding sites on both ends of the molecule, and induce folding of the molecule to form U-shaped folding, thus mimicking the natural β-turn structure.
Finally, we preliminarily studied the ability of the target molecule to form β-rurn molecular simulators by nuclear magnetic resonance technology. The results show that the molecule can indeed fold under the drive of hydrogen bonds, making it appear like a β-turn conformation.