碳核友的多种体反应概况
Vinayak Gupta1, Jing Yang2, Daniel C Liebler3
1Department of Chemistry, The Scripps Research Institute , Jupiter, Florida 33458, United States.
Journal of the American Chemical Society
|March 31, 2017
概括
我们开发了基于碳的新型核片, 这些碎片与氧化氨酸残留物反应,将药物发现扩展到"氧化还原体",并协助对氧化还原体调节的研究.
科学领域:
- 医学化学
- 化学生物学
- 蛋白质组学
背景情况:
- 有针对性的共价抑制剂在药物发现中至关重要,通常针对特定的疾病相关途径.
- 基于碎片的连接体发现 (FBLD) 扩大了可连接蛋白的范围.
- 传统的FBLD依赖于囊反应碎片,但癌症等疾病中的囊氧化限制了这种方法.
研究的目的:
- 开发一种针对氧化半氨酸残留物的共价配体发现的新方法.
- 通过对结肠癌细胞蛋白质进行查.
- 识别新的共价配体并研究它们的反应性和准偏好.
主要方法:
- 开发一个新的基于碳的核片段库.
- 使用基于片段的共价配体发现对结肠癌细胞蛋白质进行选.
- 分析已识别的共价配体-蛋白相互作用,包括反应性概况和目标偏好.
主要成果:
- 在可用药和孤儿蛋白中确定了超过1280个S-硫化囊的共价配体.
- 在C核友碎片中揭示了不同的反应概况和目标偏好.
- 发现了一种选择性地向蛋白质酸酶的 pyrrolidinedione 核素.
结论:
- 使用C核友的基于碎片的共价配体发现提供了对可连接的"redoxome"的全面视图.
- 这种方法对开发共价抑制剂和理解疾病中氧化还原调节具有重要意义.
- 提供了新的化学工具来研究氧化还原变化的蛋白质功能.
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