胺在螺旋结构中的胺的结行为
Emily A O'Brien1, Jeffrey A Purslow1, Brendan J Wall1
1Department of Chemistry, Iowa State University Ames IA 50011 USA bvv@iastate.edu.
Chemical science
|October 31, 2024
概括
氨基酸,氨基酸键异体,首次在螺旋中进行了探索. 它们通过键和盐桥来支持螺旋结构,显示了类药物设计的潜力.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 药用化学 医学化学
背景情况:
- 氨基酸键是结构的基础.
- 阿米丁是胺键异体,但在二次结构中尚未探索.
- 了解异对于改和药物设计至关重要.
研究的目的:
- 为了研究在折叠的螺旋体中氨基酸的结构作用.
- 探索基结合和稳定能力的阿米丁在背骨.
- 评估阿米丁对二次结构和C端稳定性的影响.
主要方法:
- 含有阿米丁的结构的计算建模和分析.
- 对结合模式和盐桥形成的研究.
- 在酸骨架内对胺基性质的表征.
主要成果:
- 阿米丁与螺旋状的二次结构兼容.
- 氨基酸的前基状态适应局部相互作用,形成强键并稳定盐桥.
- 酸骨架中的氨基酸的基本性低于小分子中的基本性.
- 沿着骨稳定螺旋折叠的C端的盐桥的第一个例子.
结论:
- 阿米丁可以成功地被纳入螺旋体,维持和稳定二级结构.
- 阿米丁的独特特性,包括可适应的蛋白质状态和修改的基本性,为基因工程提供了新的途径.
- 这些发现突出了胺在类药物设计中的潜力,以提高稳定性和新的相互作用.
相关概念视频
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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’...
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Physical Properties of Amines
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Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
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Hydrogen Bonds
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A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another polar molecule, such as water (H2O), hydrogen fluoride (HF), or ammonia (NH3). The huge electronegativity difference between the H atom (2.1) and the atom to which it is bonded (4.0 for an F atom, 3.5 for an O atom, or 3.0 for an N atom), combined with the very small size of an H atom...
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Basicity of Aliphatic Amines
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Amines can behave as Brønsted–Lowry bases by accepting a proton from the acid to form corresponding conjugate acids. Due to a lone pair of nonbonding electrons, aliphatic amines can also act as Lewis bases by forming a covalent bond with an electrophile.
To measure the basicity of amines, two conventions are generally used. The first defines Kb as the basicity constant for the deprotonation reaction of water by the amine, as presented in Figure 1. Conventionally, lower Kb indicates...
To measure the basicity of amines, two conventions are generally used. The first defines Kb as the basicity constant for the deprotonation reaction of water by the amine, as presented in Figure 1. Conventionally, lower Kb indicates...
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Basicity of Heterocyclic Aromatic Amines
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Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).
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NMR Spectroscopy Of Amines
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In proton NMR spectroscopy, primary amines and secondary amines showcase their N–H protons as a broad signal in the chemical shift range between δ 0.5 and 5 ppm. The exact position in this range depends on several factors, including sample concentration, hydrogen bonding, and the type of solvent used. Since amine protons undergo fast proton exchange in solution, the protons are labile and therefore do not participate in any splitting with adjacent protons. Thus, the observed peak is...
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