Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain; BioFarma, Universidad de Santiago de Compostela (USC), Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), A Coruña 15782, Spain.
Fundación Pública Galega de Medicina Xenómica (FPGMX), Servizo Galego de Saúde (SERGAS), Instituto de Investigaciones Sanitarias (IDIS), A Coruña 15706, Spain.
Bioorg Med Chem. 2021 Jun 15;40:116178. doi: 10.1016/j.bmc.2021.116178. Epub 2021 Apr 27.
The output of an affinity selection screening results in a huge amount of valuable data that, after conducting the appropriate analysis, lead to the correct identification of the compounds enriched in the target of interest. The approach chosen to perform these analyses has become a key step in the development of a successful DNA Encoded Library platform. In this paper, we describe the combination of High Performance Liquid Chromatography purification during the library production with the Next Generation Sequencing analysis of the libraries to assess the yield of the chemical reactions prior to the affinity selection. This process allows us, apart from achieving higher quality libraries, to enable a normalization analysis of the affinity selection output, thus minimizing the bias induced by the chemical yield of each reaction as a misleading factor within the analysis and subsequent compound short-listing for off-DNA synthesis.
亲和选择筛选的输出结果产生了大量有价值的数据，经过适当的分析后，可以正确识别出目标化合物中富集的化合物。选择进行这些分析的方法已成为成功开发 DNA 编码文库平台的关键步骤。在本文中，我们描述了在文库生产过程中结合高效液相色谱纯化与文库的下一代测序分析，以评估亲和选择前化学反应的产率。这个过程不仅可以使文库质量更高，还可以对亲和选择输出进行归一化分析，从而最小化每个反应的化学产率作为分析中的误导因素，并随后对非 DNA 合成的化合物进行短名单筛选。
