揭示了Sanguinarine与β-Lactoglobulin蛋白质的 iminium 和 alkanolamine 形式的不同相互作用模式
Jyoti Vishwakarma1, Sudhanshu Sharma1, Dineshbabu Takkella1
1Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Telangana 502284, India.
International journal of biological macromolecules
|November 20, 2024
概括
这项研究比较了两种形式的血红蛋白 (SANG) 与β-乳糖球蛋白 (β-LG) 蛋白的相互作用. 结果显示了不同的结合 afinities 和结构变化,为药物开发提供了洞察力.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 材料科学 材料科学 材料科学
背景情况:
- 血氨酸 (SANG) 是一种已知具有治疗功能的类化合物.
- β-乳糖球蛋白 (β-LG) 是牛奶中的主要乳清蛋白,经常被用于药物输送应用.
- 了解药物蛋白相互作用对于开发有效的治疗方法和药物输送系统至关重要.
研究的目的:
- 为了比较地研究两种分体形式的血红素 (SANG) 与β-乳球蛋白 (β-LG) 的结合相互作用.
- 阐明在SANG相互作用时诱导β-LG的结合亲和力,热力学参数和构造变化.
- 使用计算建模验证蛋白质药物复合物的稳定性.
主要方法:
- 使用光谱技术 (光,圆形二重化) 来研究SANG-β-LG相互作用.
- 使用温度依赖的光谱法来确定热力学参数.
- 进行了分子对接和分子动力学 (MD) 模拟,以分析复合物的结合模式和稳定性.
主要成果:
- 光谱分析表明,SANG的类胺形式在pH 9时与单体β-LG结合的结合亲和力更高,相比之下,iminium形式在pH 6.2时与二元β-LG结合的结合亲和力更高.
- 循环二元化揭示了β-LG的二级结构的显著变化,从α-螺旋转向β-片的过渡.
- MD模拟证实了200个纳秒的稳定蛋白-药物复合物的形成,验证了结合相互作用.
结论:
- 血红素的两种分体形式表现出与β-LG不同的相互作用模式和亲和关系.
- 这项研究为SANG-β-LG复合体形成提供了宝贵的见解,与药理学研究相关.
- 这些发现支持β-LG作为携带器用于涉及血液的药物输送系统的潜在用途.
相关概念视频
Aldehydes and Ketones with Amines: Imine Formation Mechanism
5.3K
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
5.3K
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
4.4K
Primary amines react with carbonyl compounds—aldehydes and ketones—to generate imines. Imines consist of a C=N double bond and are named Schiff bases after its discoverer—the German chemist Hugo Schiff. On the other hand, secondary amines react with carbonyl compounds to give enamines. In enamines, the presence of a C=C double bond adjacent to the nitrogen atom leads to the delocalization of the lone pair.
4.4K
Aldehydes and Ketones with Amines: Enamine Formation Mechanism
5.3K
Enamine formation involves the addition of carbonyl compounds to a secondary amine through a series of reactions. The mechanism begins with the generation of carbinolamine, a nucleophilic attack followed by several proton transfer reactions. The hydroxyl group of the carbinolamine is converted into water to make a better leaving group that can push the reaction forward by eliminating a water molecule. In enamine formation, the last step involves the abstraction of a proton from the α carbon to...
5.3K
Amines to Sulfonamides: The Hinsberg Test
3.2K
The Hinsberg test is a method to identify primary, secondary and tertiary amines, named after its pioneer, Oscar Hinsberg. Here, amines are treated with benzenesulfonyl chloride, also known as the Hinsberg reagent, in the presence of an excess of aqueous base, followed by acidification. Based on the nature of the amines, different changes are observed.
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing...
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing...
3.2K
Basicity of Aliphatic Amines
5.7K
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...
5.7K
Drug Binding to Blood Components
112
When drugs enter systemic circulation, they interact with various components of the blood, including proteins such as human serum albumin (HSA), α1-acid glycoprotein (AAG), lipoproteins, globulins, and red blood cells (RBCs).
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are...
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are...
112


