Dolle R E
Department of Chemistry, Pharmacopeia Inc., Princeton, NJ 08540, USA.
Mol Divers. 1997;2(4):223-36. doi: 10.1007/BF01715638.
This review serves to highlight the recent examples of combinatoric methodology as applied to the discovery and optimization of enzyme inhibitors. Early research efforts focused on the identification of polypeptides from libraries as inhibitors of proteases. As solution- and solid-phase chemistries gain in sophistication, libraries containing less peptidic structural motifs have been created. A recurring design stratagem relies on the synthesis of libraries incorporating pharmacophores with known affinity for the target enzyme. Screening of these structure-based libraries has led to the discovery of small-molecule inhibitors of both proteolytic and non-proteolytic enzymes alike. Two tables are provided listing the enzyme targeted libraries through 1996. A name, generic structure and size is given for each library citation, accompanied by the enzyme screen and the structure and potency of the most active library member.
本综述旨在突出组合方法学在酶抑制剂发现和优化中的最新应用实例。早期的研究工作集中于从文库中鉴定多肽作为蛋白酶抑制剂。随着溶液和固相化学技术的日益成熟，已创建了包含较少肽类结构基序的文库。一种反复使用的设计策略依赖于合成包含对目标酶具有已知亲和力的药效团的文库。对这些基于结构的文库进行筛选，已发现了蛋白水解酶和非蛋白水解酶的小分子抑制剂。提供了两个表格，列出了截至1996年的靶向酶文库。每个文库引用都给出了名称、通用结构和大小，同时列出了酶筛选结果以及最具活性的文库成员的结构和效力。
