利用亲和选择筛选法从组合化学库中筛选新药  

Using Affinity Selection to Screen New Drugs in Combinatorial Libraries

作　　者：吴增茹[1] 徐筱杰[1] 

机构地区：[1]北京大学化学与分子工程学院,北京100871

出　　处：《分析化学》2002年第1期101-106,共6页Chinese Journal of Analytical Chemistry

摘　　要：组合化学方法可以产生大量的新化合物供新药筛选，但传统的逐一筛选法不能满足如此数量庞大的化合物。因此，针对混合物进行筛选显得非常重要。亲和选择筛选法利用药物作用的靶蛋白与潜在药物之间的亲和活性，使目标化合物与大量无亲和活性的化合物分离，然后只对有亲和活性的化合物进行结构鉴定，从而快速地从大量混合物中找到目标化合物。本文着重讨论了亲和选择筛选的几种形式、相应技术和在组合化学库筛选中的应用。亲和选择筛选大体分为两种方式：一种是将靶蛋白固定在支持物上，有亲和活力的化合物被保留，大量非亲和化合物被洗掉；另一种是在溶液中靶蛋白与混合物库孵育，然后利用受体配基复合物与不结合的游离化合物性质的差别进行区分。亲和选择筛选法也适合于化合物的种类和含量都未知的天然提取物的筛选。The method of combinatorial. chemistry can provide a large amount of new compounds to screen new drugs, so it is important to screen mixture while the traditional parallel discrete assays can not meet the demand. Compounds which produce biological activity by binding receptor must have affinity to receptor. Based on this property, the biological active compounds can be seperated from the large amount of other compounds. Affinity selection can find the target compounds quickly by identifying the compounds retained by the receptor. The article reviews the forms of the affinity selection screening, its related techniques and application in screening combinatorial libraries. Affinity selection has two main forms: in the first one, the receptor is immobilized to the solid support while retains the target compounds meanwhile the others would be washed off; in the second one, the target protein is incubated with the mixture in solution, and the complexes have great difference from the small moleculars. Affinity selection is also a suitable method in screening natural product extracts in which the components and their amount remain largely unknown.

关 键 词：组合化学库 亲和选择 药物筛选 药物化学 固定化靶蛋白 新药开发 亲和选择色谱 

分 类 号：TQ460[化学工程—制药化工]