一种基于的新型编码系统,用于"一珠一化合物"的二模和小分子组合库
Ruiwu Liu1, Jan Marik, Kit S Lam
1Division of Hematology & Oncology, Department of Internal Medicine, UC Davis Cancer Center, University of California-Davis, 4501 X Street, Sacramento, CA 95817, USA.
Journal of the American Chemical Society
|June 27, 2002
概括
一个新的基于的编码系统简化了"一珠一化合物" (OBOC) 库的结构确定. 这种方法有效地识别来自大型组合图书馆的强大,新型联体.
科学领域:
- 药用化学 医学化学
- 组合化学 组合化学
- 生物技术是生物技术.
背景情况:
- "一珠一化合物" (OBOC) 方法使数百万种化合物的高通量选成为可能.
- 通过OBOC方法合成的化合物的结构确定,特别是二和小分子,存在重大挑战.
研究的目的:
- 为 OBOC 组合图书馆开发一种新,高效和强大的基于的编码系统.
- 克服在OBOC查中对二甲基和小分子的结构确定方面的局限性.
主要方法:
- 使用了使用双相溶剂策略创建的拓分离的双功能珠.
- 开发了一种基于的编码标签,包含非天然的α-氨基酸,与测试化合物同时合成.
- 采用埃德曼降解来直接测序没有裂变的正珠.
主要成果:
- 成功生成并选了一个158,400个成员编码的代体图书馆.
- 鉴定出具有独特动机的强效和新联体,它们与链状维丁结合.
- 证明了基于的编码系统的效率和简单性.
结论:
- 开发的基于的编码系统对于 OBOC 组合图书馆来说是非常高效和强大的.
- 这种方法简化了结构的确定,并促进了新生物活性化合物的发现.
- 该系统消除了额外的合成步骤,并最大限度地减少了不必要的副产品.
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