DNA-encoded chemical library (DECL) synthesis must occur in aqueous media under conditions that preserve the integrity of the DNA encoding tag. While the identification of "DNA-compatible" reaction conditions is critical for the development of DECL designs that explore previously inaccessible chemical space, reports measuring such compatibility have been largely restricted to methods that do not faithfully capture the impact of reaction conditions on DNA fidelity in solution phase. Here we report a comprehensive methodology that uses soluble DNA substrates that exactly recapitulate DNA's exposure to the chemically reactive species of DECL synthesis. This approach includes the assessment of chemical fidelity (reaction yield and purity), encoding fidelity (ligation efficiency), and readability (DNA compatibility), revealing the fate of the DNA tag during DECL chemistry from a single platform.

中文翻译：

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用于表征化学反应与 DNA 编码化学库合成的兼容性的溶液相平台。

DNA 编码化学文库 (DECL) 的合成必须在水性介质中、在保持 DNA 编码标签完整性的条件下进行。虽然“DNA 相容”反应条件的识别对于开发 DECL 设计（探索以前无法进入的化学空间）至关重要，但测量这种相容性的报告在很大程度上仅限于不能忠实捕捉反应条件对 DNA 保真度影响的方法。溶液阶段。在这里，我们报告了一种综合方法，该方法使用可溶性 DNA 底物，准确地概括了 DNA 暴露于 DECL 合成化学反应物质的情况。该方法包括评估化学保真度（反应产率和纯度）、编码保真度（连接效率）和可读性（DNA 兼容性），从而从单一平台揭示 DECL 化学过程中 DNA 标签的命运。