光标签可以显著扰乱测量的-蛋白相互作用的结合亲和力和选择性
Sara Bobone1, Claudia Storti1,2, Chiara Fulci1
1Tor Vergata University of Rome, 00133 Rome, Italy.
The journal of physical chemistry letters
|October 3, 2024
概括
光标签可以改变类药物结合亲和力,导致蛋白质-蛋白质相互作用试验的结果不准确. 未标记的精确地揭示了SHP2抑制剂的高向性和低非向性结合.
科学领域:
- 生物化学 生物化学
- 化学生物学 化学生物学
- 药物发现 药物发现 药物发现
背景情况:
- 基于的药物是蛋白质-蛋白质相互作用的有效抑制剂.
- 基于光的测定,如异性异性和微阵列是评估药物结合的常见方法.
- 标签策略可能会在这些测试中引入文物.
研究的目的:
- 为了研究光标签对酸/蛋白质结合亲和力的影响.
- 为了验证针对SHP2 N-终端Src同质2 (SH2) 域的新抑制剂的选择性.
- 在药物发现中识别和减轻测试文物.
主要方法:
- 开发针对 SHP2 SH2 域的抑制剂.
- 使用光异性和定量微阵列来评估结合亲和力.
- 使用标记和未标记的结合 afinities 的比较.
主要成果:
- 光标签扰乱了/蛋白质结合超过一个数量级.
- 不同性测量显示,标记显著影响解离常数 (∼10倍).
- 使用未标记的排位测试证实,抑制剂对SHP2的亲和力是APS的1000倍以上.
结论:
- 光标签可以显著影响基药物的测量亲和力和选择性.
- 未标记的位测试对于准确评估药物向相互作用至关重要.
- 新型SHP2抑制剂在控制人工物时表现出高亲和力和选择性.
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