用DNA编码的动态化学库及其在结体发现中的应用
Yu Zhou1,2, Chen Li1, Jianzhao Peng2,3
1Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology , Peking University Shenzhen Graduate School , 2199 Lishui Road West , Shenzhen 518055 , China.
Journal of the American Chemical Society
|November 10, 2018
概括
这项研究引入了一种基于DNA的新策略,以克服动态组合图书馆 (DCL) 的局限性,使生物医学研究能够发现小分子对. 这种方法增强了库的多样性和分析能力,以有效地识别连接物.
科学领域:
- 生物化学
- 医学化学
- 化学生物学
背景情况:
- 动态组合图书馆 (DCL) 对联体发现具有强大作用,但由于其低多样性和分析挑战而受到限制.
- 现有的DCL方法难以处理大型复杂的库以有效识别目标.
研究的目的:
- 从大规模的DCL中选择合作结合的小分子对.
- 解决DCL应用中的图书馆多样性和分析处理的局限性.
主要方法:
- 使用DNA介导的动态杂交和DNA编码.
- 实施基于照片交叉链接的解码方案进行分析.
- 构建并对六个蛋白质目标进行了1万个成员的DNA编码动态库的选.
主要成果:
- 成功地确定了六种蛋白质目标中的每一个特定的小分子结合剂.
- 验证了所选配体的生物活性,包括那些参与蛋白质脱乙和化.
- 开发了新的选择性Sirtuin-3抑制剂,证明了该方法的有效性.
结论:
- 开发的策略绕过了DCL的主要障碍,显著提高了连接物发现能力.
- 这种方法提供了一个广泛适用的方法来识别对不同的生物点的配体.
- 这些发现为使用先进的DCL技术更有效地发现和开发药物铺平了道路.
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