α-Hydrazino 酸插入通过局部结构排序来控制溶液中的组织
Luka Kavčič1, Gregor Ilc1,2, Baifan Wang1
1Slovenian NMR Centre, National Institute of Chemistry, Ljubljana 1000, Slovenia.
ACS omega
|May 27, 2024
概括
将α-hydrazino酸引入中可以为蛋白质-蛋白质相互作用 (PPI) 抑制剂创建稳定的结构. 这种修改增强了的适应性和药物开发的结构空间.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 药用化学 医学化学
背景情况:
- 蛋白与蛋白相互作用 (PPI) 在细胞过程中至关重要.
- 开发用于PPI的小分子抑制剂仍然具有挑战性.
- 了解的结构动力学是抑制剂设计的关键.
研究的目的:
- 为了研究将α-hydrazino酸纳入的结构影响.
- 探索酸作为蛋白质-蛋白质相互作用抑制剂的潜力.
- 在溶液中模拟由化修饰引起的构造变化.
主要方法:
- 在序列中应用α-酸插入的应用.
- 核磁共振 (NMR) 光谱用于结构分析.
- 计算建模用于生成结构假设.
主要成果:
- 氨酸修饰诱导局部结构 (α-, β-, γ-转).
- 引入额外的原子改变了静电特性和键.
- 观察到快速相互转换的构造,包括E-Z化物异构化,扩大构造适应性.
结论:
- α-hydrazino 酸的结合为的结构组织提供了一种策略.
- 氨酸显示了预先组织成有利于受体结合的螺旋结构的潜力.
- 酸的扩大形态空间增强了它们作为PPI对手的效用.
相关概念视频
Protein Organization
137.3K
Overview
137.3K
Protein Folding
8.0K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.0K
Amyloid Fibrils
9.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.5K
Protein and Protein Structure
79.4K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
79.4K
Intrinsically Disordered Proteins
17.8K
Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
17.8K
Structure of Amines
2.5K
The hybridized nitrogen atom in amines possesses a lone pair of electrons and is bound to three substituents with a bond angle of around 108°, which is less than the tetrahedral angle of 109.5°. However, the C–N–H bond angle is slightly larger at 112°, with a carbon–nitrogen bond length of 147 pm. This carbon–nitrogen bond length of of amines is longer than the carbon–oxygen bond of alcohols (143 pm) but shorter than alkanes’...
2.5K


