四值和六值的Siglec-8干调节免疫细胞激活
Gabriele Conti1,2, Anne Bärenwaldt3,4, Said Rabbani1
1Molecular Pharmacy Group, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.
Angewandte Chemie (International ed. in English)
|November 10, 2023
概括
性配体可以有效地与免疫细胞上的Siglec-8 (酸结合性免疫球蛋白类似的lectin 8) 结合,调节它们的激活. 即使是低的寡值也可以触发生物效应,与单价联体不同.
科学领域:
- 碳水化合物-蛋白质相互作用
- 免疫学 免疫学 免疫学
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 碳水化合物结合蛋白通常表现出低亲和力,这是由于浅,暴露于溶剂的结合部位.
- 大自然利用多价值来增强通过多个表位的同时参与的结合相互作用.
研究的目的:
- 合成和热力学表征Siglec-8 (酸结合性免疫球蛋白类讲蛋白8) 的寡价联体.
- 研究这些连接体调节免疫细胞激活的潜力.
主要方法:
- 合成针对Siglec-8.8的各种寡值配体.
- 对联体蛋白结合的热力学分析.
- 评估Siglec-8结合和免疫细胞激活调节对乙氨基和巨细胞的作用.
主要成果:
- 结合性亲和力随着连接物价值的增加而增强,随着热惩罚的增加.
- 四价值,六价值和多价值连接体在免疫细胞上对Siglec-8表现出agonistic的结合.
- 低寡性联结体诱导了生物效应,而单性联结体尽管具有相似的结合亲和力,但却表现出对抗性的效应.
结论:
- 寡性是一种成功的策略,可以增强Siglec-8的结合和功能.
- 连接物性影响着结合热力学和生物活性 (激动与对抗).
- 低寡值配体可以触发Siglec-8介导的免疫细胞反应.
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