Highly sensitive in vitro selections for DNA-linked synthetic small molecules with protein binding affinity and specificity
Highly sensitive in vitro selections for DNA-linked synthetic small molecules with protein binding affinity and specificity
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DOI：
10.1021/ja036065u
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发表时间：
2003-10-15
影响因子：
15
通讯作者：
Liu, DR
中科院分区：
文献类型：
--
作者：
Doyon, JB;Snyder, TM;Liu, DR
我们已经开发出具有蛋白质结合亲和力和特异性的dna连接合成小分子的体外选择。这些选择只需要一般可获得的设备，从主要是非活性物种的混合物中提供高度富集的活性分子，可以应用于各种不相关的蛋白质，并且比现有的合成分子筛选方法所需的材料少约108倍。迭代这些选择使活性分子的净富集倍数倍增，从而实现超过106的巨大总体富集因子。此外，除了结合亲和性外，所述选择还可以适应于选择结合特异性。本工作中所描述的方法的应用可能在从dna模板合成文库中发现所需分子方面发挥关键作用。
We have developed in vitro selections for DNA-linked synthetic small molecules with protein binding affinity and specificity. These selections require only generally accessible equipment, offer high degrees of enrichment of active molecules from mixtures of predominantly inactive species, can be applied to a variety of unrelated proteins, and require approximately 108-fold less material than existing synthetic molecule screening methods. Iterating these selections multiplies the net enrichment of active molecules, enabling enormous overall enrichment factors exceeding 106to be achieved. Further, the selections can be adapted to select for binding specificity in addition to binding affinity. The application of methods described in this work may play a key role in the discovery of desired molecules from DNA-templated synthetic libraries.