半合成人体白蛋白异型:生产,结构,结合能力和对例行实验室测试的影响
Roy Lakis1, François-Ludovic Sauvage1, Emilie Pinault1
1P&T, UMR1248, University of Limoges, National Institute for Health and Medical Research (INSERM), Limoges, France.
International journal of biological macromolecules
|August 12, 2023
概括
使用半合成方法制造的人类血清白蛋白 (HSA) 异型,显示出改变的结合活性. 这些特征化的异构体对研究疾病生物标志物和白蛋白量化挑战有价值.
科学领域:
- 生物化学 生物化学
- 分析化学 分析化学
- 生物标志物发现发现
背景情况:
- 人类血清白蛋白 (HSA) 存在于各种异构形式,由于后翻译性修改 (PTMs).
- 在糖尿病,脏和肝脏疾病等疾病中,HSA异型的丰富程度会发生变化.
- 了解单个异构体的影响对于识别病原性和潜在的生物标志物实用性至关重要.
研究的目的:
- 创建和表征半合成HSA异型.
- 研究个别HSA异型的结构和功能性质.
- 评估HSA异型对常规白蛋白量化方法的影响.
主要方法:
- 半合成制备的HSA异型 (乙化,cysteinylated,氧化,化,糖化).
- 先进的质谱学 (LC-TOF-MS,ICP-MS) 用于结构特征.
- 结合能力测试用于连接物相互作用和抗氧化剂活性评估.
- 评估用于异构体量化的免疫度测定试验.
主要成果:
- 成功生成了具有高纯度的半合成HSA异型.
- 证明了异形的各种连接体 (例如,Cu,Cd,Au,Ds,L-T4) 的改变结合能力.
- 发现免疫度测试对不同HSA异型的存在和丰度不敏感.
结论:
- 特征化半合成HSA异型为进一步研究提供了有价值的工具.
- 这些异构体可以用来研究它们的特定致病性.
- 这些发现凸显了对异构体特异性试验的需要,以准确量化白蛋白和生物标志物开发.
相关概念视频
01:29Drug Distribution: Plasma Protein Binding
5.7K
Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
5.7K
01:20Factors Affecting Protein-Drug Binding: Protein-Related Factors
192
Drug binding to proteins is a key aspect of pharmacokinetics and can influence a drug's distribution, absorption, and elimination in the body. Several factors, including the drug's physiochemical properties, protein concentration, disease states, and the number of binding sites on the protein, influence this process.
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
192
01:29Factors Affecting Protein-Drug Binding: Patient-Related Factors
82
Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
82
01:18Factors Affecting Protein-Drug Binding: Drug-Related Factors
141
Drug binding to proteins is a complex phenomenon influenced by various drug-related factors, each playing a significant role in the interaction between drugs and proteins within the body.
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...
141
01:30Drug Binding to Blood Components
174
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...
174
01:22Protein-Drug Binding: Determination Methods
238
Determining protein-drug binding can be achieved through indirect and direct methods, each providing valuable insights into the interaction between proteins and drugs.
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
238