激活蛋白C类功能通过通过单个氨基酸差异的抗体进行不同的调节
Derek S Sim1, Meenal Shukla2, Cornell R Mallari1
1Coagulant Therapeutics Corporation, Berkeley, CA.
Blood advances
|October 29, 2024
概括
针对活性蛋白C (APC) 的抗体可以选择性地调节其功能. 对TPP-26870的亲和力成熟表明,单个突变改变了APC.
科学领域:
- 生物化学 生化学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 活性蛋白C (APC) 是一种具有抗凝固,抗炎和细胞保护作用的关键蛋白酶.
- 通过抗体调节APC活性为诸如败血症和创伤等疾病提供了治疗潜力.
- TPP-26870是一种抗体,旨在通过向非活性部位来选择性地改变APC功能.
研究的目的:
- 为了优化APC向抗体TPP-26870.的功效.
- 研究单氨基酸突变在互补性决定区域 (CDR) 对TPP-26870与APC相互作用的影响.
- 了解表皮层-CDR相互作用如何影响APC的类活动.
主要方法:
- 在CDR中选具有单氨基酸突变的TPP-26870变体.
- 亲和度成熟以识别与APC结合改善的变体.
- 功能性测试用于评估突变抗体对各种APC活动 (例如抗凝剂,组蛋白H3裂变,PAR1裂变) 的影响.
主要成果:
- 确定了21种TPP-26870的变种,具有增强的结合亲和力与APC.
- 证明CDR中的单氨基酸突变可以导致对APC功能产生不同的对抗和对抗作用.
- 观察到APC的血半衰期,抗凝固剂抑制和基因素H3裂变的显著变化,对PAR1裂变的影响最小.
结论:
- APC对非活跃网站准具有高度敏感性,导致其活动概况发生不可预测的变化.
- 抗体工程可以精确地修改APC功能,突出了开发APC向治疗的潜力.
- 这些发现支持APC向抗体的发展,用于治疗诸如创伤出血,血友病,缺血症和败血症等疾病.
更多相关视频
11:10Antibody Binding Specificity for Kappa (Vκ) Light Chain-containing Human (IgM) Antibodies: Polysialic Acid (PSA) Attached to NCAM as a Case Study
Published on: June 29, 2016
14.0K
07:26High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
Published on: July 18, 2017
11.8K
相关概念视频
Cross-reactivity
31.0K
Overview
31.0K
Protein Complexes with Interchangeable Parts
2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K
Antibody Structure
59.3K
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...
59.3K
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
Antibody Actions
1.1K
Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
1.1K
Conservation of Protein Domains Over Different Proteins
10.8K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
10.8K
