用单克隆抗体准RAGE的硫酸肝素结合部位
Chihyean Ong1, Miaomiao Li1, Ding Xu1
1Department of Oral Biology, School of Dental Medicine, University at Buffalo, the State University of New York, 3435 Main Street, Buffalo, NY 14214, United States.
Glycobiology
|January 5, 2024
概括
开发针对像RAGE这样的蛋白质的肝素硫酸盐 (HS) 结合部位的抗体是可行的. 这些抗体显示HS蛋白相互作用和下游功能的不同抑制,表明治疗潜力.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 肝硫酸盐 (HS) 通过调解相互作用,对许多细胞外和膜外蛋白的功能至关重要.
- 先进的糖化最终产品 (RAGE) 激活的受体取决于HS诱导的寡合化,突出显示HS结合部位的重要性.
研究的目的:
- 提出一种开发和表征针对RAGE的HS结合部位的单克隆抗体 (mAbs) 的方法.
- 调查HS结合部位的免疫性和产生的mAbs.特征.
主要方法:
- 反RAGE mAbs. 的开发和表征.
- 对抗HS结合部位mAbs.的表皮图绘制和序列分析.
- 评估HS-RAGE相互作用的抑制和骨质细胞形成的抑制.
主要成果:
- 在94种抗RAGE mAbs中,有18种针对HS结合部位,表明其免疫性.
- 抗HS结合位点mAbs在它们的互补性决定区域中经常存在酸性残留物,这表明了静电相互作用.
- 针对HS结合部位内的不同表位的mAbs表现出不同程度的HS-RAGE相互作用和骨质细胞形成的抑制,独立于简单的亲和关系相关性.
结论:
- 开发HS结合位点向mAbs的工作流程广泛适用于其他HS结合蛋白.
- 用mAbs准HS结合部位为涉及HS结合蛋白的疾病提供了潜在的治疗策略.
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