设计小型绑定蛋白质作为对抗犬类和人类TNFα的通用抗体
Jun Weng1,2,3, Zhiyong Wu1,2, Banbin Xing1,2
1State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
Communications biology
|November 25, 2025
概括
研究人员开发了在狗和人类中有效的通用TNFα对抗剂. 这些新型生物药物准了保存的相互作用地点,提供了一个有前途的跨物种治疗方法.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤坏死因子α (TNFα) 是一种关键的炎症性细胞因子,与各种疾病有关.
- 针对TNFα的现有生物药物往往表现出特定物种的疗效,限制了它们在比较医学中的使用.
研究的目的:
- 阐明犬类TNFα (cTNFα) 与纳米体结合的结构基础.
- 确定保护的相互作用区域,以设计在犬类和人类系统中有效的通用TNFα抑制剂.
主要方法:
- 低温电子显微镜被用来确定cTNFα与纳米体结合的结构.
- 对cTNFα和人类TNFα (hTNFα) 进行了比较结构分析和分子模拟.
- 使用de novo计算设计,设计了针对保存的疏水区域的新型迷你绑定器.
主要成果:
- 该研究以3.1 Å分辨率解析了cTNFα-纳米体复合结构.
- 确定了一个关键差异 (cTNFα中的Phe83),影响了纳米体结合亲和力.
- 设计的迷你结合剂对cTNFα和htNFα都表现出高亲和力 (从亚纳米到纳米).
- 基于细胞的测定证实了两种物种强烈的抗TNFα活性.
结论:
- 确定了一个保护的疏水区域,对TNFα受体相互作用至关重要.
- 一个计算设计策略产生了有效的通用TNFα对抗剂.
- 这些发现为开发跨物种生物制剂铺平了道路,用于治疗人类和狗的炎症状况.
更多相关视频
16:07Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
9.6K
12:09Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
10.2K
相关概念视频
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
465
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
465
02:26NF-κB-dependent Signaling Pathway
9.7K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
9.7K