对抗体Fc结合物的选择性模板导向合成,同时释放连接体
Viktoriia Postupalenko1, Léo Marx2, Mathilde Pantin2
1Institute of Life Technologies, HES-SO Valais-Wallis Rue de l'Industrie 23 CH-1950 Sion Switzerland origene.nyanguile@hevs.ch.
Chemical science
|January 26, 2024
概括
研究人员开发了一种新的抗体结合方法,针对特定的氨酸位 (K248,K439) 进行精确的有效载荷传递. L6Orn-碳酸盐变体在多种抗体类型中实现了对各种有效载荷 (包括成像剂) 的高合效率.
科学领域:
- 生物结合化学 生物结合化学
- 抗体工程 抗体工程
- 分子成像学分子成像学
背景情况:
- 模板导向的结合使得特定站点的有效载荷能够附着在单克隆抗体 (mAbs) 上.
- 之前的研究使用了一种工程Fc-III反应性用于K317结合.
研究的目的:
- 重新设计Fc-III反应性方法,以准K248和K439.
- 为选择性和高效的抗体结合确定最佳的Fc-III变异.
主要方法:
- 采用能量最小化预测和半组合合成来产生Fc-III变体.
- 使用中向下MS/MS分析来确认K248和K439在trastuzumab上的选择性向.
- 评估了各种Fc-III变体的合效率和有效载荷兼容性.
主要成果:
- Fc-III变种L6Dap,L6Orn,L6Y,A3K和A3hK选择性地准了K248和K439的目标.
- L6Orn-碳酸盐在各种有效载荷中表现出高的结合度 (~2) 和产量 (~100%).
- L6Orn-碳酸盐在多种IgG亚型中显示出一致的结果.
- 在体内成功地对PD-L1表达进行PET成像,使用[64Cu]Cu-atezolizumab.
结论:
- 重新设计的Fc-III方法可以在K248和K439.9进行特定地点的结合.
- L6Orn-碳酸盐是一种高效和多用途的抗体-药物合剂和成像剂的结合试剂.
- 这种方法有助于有针对性的*in vivo*成像和治疗应用.
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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
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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.
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