Wilson-Lingardo L, Davis P W, Ecker D J, Hébert N, Acevedo O, Sprankle K, Brennan T, Schwarcz L, Freier S M, Wyatt J R
ISIS Pharmaceuticals, Carlsbad, California 92008, USA.
J Med Chem. 1996 Jul 5;39(14):2720-6. doi: 10.1021/jm960169g.
An experimental evaluation of several different pooling strategies for combinatorial libraries was conducted using a library of 810 compounds and an enzyme inhibition assay (phospholipase A2). The library contained compounds with varying degrees of activity as well as inactive compounds. The compounds were synthesized in groups of three and pooled together in various formats to realize different pooling strategies. With one exception, all iterative deconvolution strategies and position scanning resulted in identification of the same compound. The results are in good agreement with the predicted outcome from theoretical and computational methods. These data support the tenet that active compounds for pharmaceutically relevant targets can be successfully identified from combinatorial libraries organized in mixtures.
使用一个包含810种化合物的文库和一种酶抑制试验（磷脂酶A2），对组合文库的几种不同汇集策略进行了实验评估。该文库包含具有不同活性程度的化合物以及无活性化合物。这些化合物以三个一组的方式合成，并以各种形式汇集在一起以实现不同的汇集策略。除了一个例外，所有迭代去卷积策略和位置扫描都导致鉴定出相同的化合物。结果与理论和计算方法预测的结果高度一致。这些数据支持这样一个原则，即可以从以混合物形式组织的组合文库中成功鉴定出与药学相关靶点的活性化合物。
