高度的三二酸盐在强迫压力条件下稳定了重组IgG1
Deepika Sarin1, Debasmita Chakraborty1, Shravan Sreenivasan1
1Department of Chemical Engineering, Indian Institute of Technology Delhi, India.
Journal of pharmaceutical sciences
|January 11, 2025
概括
较高的度可显著提高单克隆抗体在各种压力条件下对聚合的稳定性. 这项研究证明了三糖.
科学领域:
- 生物制药配方 生物制药配方
- 蛋白质稳定性与工程学
- 药物供应和稳定 药物供应和稳定
背景情况:
- 单克隆抗体 (mAbs) 需要辅助剂才能稳定.
- 三糖是生物治疗中常见的稳定剂.
- 它在不同压力下更高度的有效性需要进一步研究.
研究的目的:
- 为了评估高度 (230毫米) 的高度对液体trastuzumab稳定性的影响.
- 为了评估热,光 (有/没有H2O2),湿度和提取应力下的稳定性.
- 使用in-silico方法研究稳定机制.
主要方法:
- 强制降解研究对trastuzumab,rituximab和bevacizumab的强制降解,有或没有高度的三糖.
- 在热和光应力下高分子量 (HMW) 形成的评估.
- 在湿度和提取压力下对二级/三级结构变化的评估.
- 在中分析三糖-特拉斯图祖马布Fab结合相互作用.
主要成果:
- 在热 (4.89%与38.80%) 和光/H2O2压力下,高度的醇显著减少了trastuzumab中的HMW形成.
- 在热应力下观察到与rituximab和bevacizumab相似的稳定.
- 在湿度和提取应力下,Trehalose减轻了二级/三级结构破坏.
- 在体中进行的研究表明,随着三糖度的增加,气结合的增加,从而减少聚合.
结论:
- 较高的三糖度 (230 mM) 显著提高了mAb对聚合和结构降解的稳定性.
- 三醇在热,光,湿度和提取压力条件下提供保护.
- 增强的结相互作用解释了三醇的稳定机制.
相关概念视频
Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Polyprotic Acids
Acids are classified by the number of protons per molecule that they can give up in a reaction. Acids such as HCl, HNO3, and HCN that contain one ionizable hydrogen atom in each molecule are called monoprotic acids. Their reactions with water are:
Immunoprecipitation
Immunoprecipitation, or IP, is a widely used technique that employs protein-antibody interactions to isolate proteins or protein complexes in their native state for studying protein-protein interactions, quaternary structures, or supramolecular complexes. Various modifications of the technique, including chromatin IP, cross-linking IP, and fluorescence IP, are commonly used.
Chromatin Immunoprecipitation
Chromatin immunoprecipitation, also known as ChIP, is used to study protein-DNA or...
Chromatin Immunoprecipitation
Chromatin immunoprecipitation, also known as ChIP, is used to study protein-DNA or...
Antibody Structure and Classes
Antibodies, also known as immunoglobulins, are produced by B cells in response to foreign substances, such as bacteria and viruses. These proteins are critical for recognizing and neutralizing these substances, protecting the body from potential harm.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.


