转换编码策略加速了从单链DNA编码库中HIT验证
Sara Puglioli1, Mosè Fabbri1, Claudia Comacchio1
1R&D Department, Philochem AG, Libernstrasse 3, Otelfingen, ZH CH-8112, Switzerland.
Bioconjugate chemistry
|July 4, 2024
概括
一种新的DNA编码库 (DEL) 方法可以在选过程中精确地区分异构体. 这种方法通过改善丰富因子和简化合成来增强成功识别并简化药物发现.
科学领域:
- 药用化学 医学化学
- 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:
- 用DNA编码的图书馆 (DELs) 提供了大量复合物集合的高通量选.
- 目前的DEL构造和击中复合可能具有挑战性,特别是在立体同位素.
研究的目的:
- 为DELs引入一种新的代编码策略,在序列级别上区分异构体.
- 验证这种方法用于构建纯粹的单药孔DEL,并评估其在药物发现活动中的表现.
主要方法:
- 为单链,单药DELs开发了一个变换编码策略.
- 合成和选了一种921,600个成员的4-氨基DEL (DEL1) 和一个24个支架的循环DEL (DEL2).
- 利用高通量测序来分析选择性丰富和DNA结合亲缘关系.
主要成果:
- 德尔1选显示了强效立体同位素的选择性丰富,性能优于传统方法.
- 针对人类FAP的DEL2选发现了五种富含的循环.
- 丰富因子和DNA结合亲缘关系之间观察到直接的相关性.
结论:
- 顺序编码策略有助于DEL库合成和击中重合成.
- 这种方法增强了丰富因子,加速了候选药物的识别.
- 这种方法适用于各种应用,包括新发现和亲和力成熟.
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