Tan D S, Burbaum J J
Department of Chemistry and Chemical Biology, Institute of Chemistry and Cell Biology, Harvard University, Cambridge, MA 02138, USA.
Curr Opin Drug Discov Devel. 2000 Jul;3(4):439-53.
Solid-phase combinatorial synthesis using split-pool or direct divide methods allows large libraries of complex molecules to be generated. Encoding techniques used during synthesis allow the identities of the products to be determined readily. An overview of this process and its application to ligand discovery are presented, along with comparisons to alternative approaches. Libraries are classified depending upon their intended use as discovery libraries (for broad screening), targeted libraries (for structure-based screening) and optimization libraries (for activity improvement). Biological assays can be performed on the solid support that is used in synthesis, or in solution under in vitro or in vivo conditions, with readouts indicative of either receptor binding or biological activity. This approach has led to numerous examples of successful ligand discovery.
使用分池法或直接分割法的固相组合合成能够生成大量复杂分子文库。合成过程中使用的编码技术使得产物的身份能够轻松确定。本文介绍了这一过程及其在配体发现中的应用，并与其他方法进行了比较。文库根据其预期用途分为发现文库（用于广泛筛选）、靶向文库（用于基于结构的筛选）和优化文库（用于活性改进）。生物测定可以在合成中使用的固相支持物上进行，也可以在体外或体内条件下的溶液中进行，读出结果表明受体结合或生物活性。这种方法已经产生了许多成功的配体发现实例。
