High-throughput sequencing for the identification of binding molecules from DNA-encoded chemical libraries
High-throughput sequencing for the identification of binding molecules from DNA-encoded chemical libraries
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DOI：
10.1016/j.bmcl.2010.05.053
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发表时间：
2010-07-15
影响因子：
2.7
通讯作者：
Neri, Dario
中科院分区：
文献类型：
--
作者：
Buller, Fabian;Steiner, Martina;Neri, Dario
DNA编码的化学文库是小的有机分子的大集合，单独地耦合到DNA片段，作为可重复的识别条形码。特异性结合剂的分离需要在捕获到固定的目标靶蛋白之前和之后定量分析文库中DNA片段的分布。在这里，我们展示了Illumina测序如何应用于DNA编码的化学文库的分析，每个泳道产生超过1000万个DNA序列标签。该技术可以以多重格式使用，允许在同一实验中对多个选择进行编码和后续测序。发现DNA编码的化学文库选择中的序列分布与使用454技术获得的序列分布相似，从而加强了DNA测序是文库选择解码的适当途径的概念。使用Illumina方法获得的大量序列现在能够研究非常大的DNA编码的化学文库（> 500，000种化合物）并降低解码成本。(C)2010爱思唯尔有限公司版权所有。
DNA-encoded chemical libraries are large collections of small organic molecules, individually coupled to DNA fragments that serve as amplifiable identification bar codes. The isolation of specific binders requires a quantitative analysis of the distribution of DNA fragments in the library before and after capture on an immobilized target protein of interest. Here, we show how Illumina sequencing can be applied to the analysis of DNA-encoded chemical libraries, yielding over 10 million DNA sequence tags per flow-lane. The technology can be used in a multiplex format, allowing the encoding and subsequent sequencing of multiple selections in the same experiment. The sequence distributions in DNA-encoded chemical library selections were found to be similar to the ones obtained using 454 technology, thus reinforcing the concept that DNA sequencing is an appropriate avenue for the decoding of library selections. The large number of sequences obtained with the Illumina method now enables the study of very large DNA-encoded chemical libraries (>500,000 compounds) and reduces decoding costs. (C) 2010 Elsevier Ltd. All rights reserved.