We report the design and synthesis of a DNA-encoded one-bead one-compound library of cyclic peptoids composed of more than 11 million molecules. We show that affinity-based screening of this large library can identify cyclic peptoid ligands for a target protein. In this work, we developed a simple method for amplifying the PCR product from DNA tags on a single bead, thereby enabling determination of the structures of hit cyclic peptoids with no need for high-throughput sequencing and complicated data analysis. We also developed a sublibrary screening strategy to minimize false positives caused by the interference of coding DNA tags before starting laborious and impractical hit confirmation. Given the simplicity and robustness of the synthesis and screening, along with the desirable features of macrocyclic peptoids including improved conformational rigidity, our method will be highly useful for discovering biologically active molecules modulating challenging targets such as protein-protein interactions that are not easily targeted by typical peptidomimetics and small-molecules.

中文翻译：

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大环类肽的DNA编码组合文库。

我们报告了由超过1100万个分子组成的环状类肽的DNA编码的单珠单化合物文库的设计与合成。我们表明，基于亲和力的这个大库的筛选可以识别目标蛋白的环状类肽配体。在这项工作中，我们开发了一种从单个珠子上的DNA标签扩增PCR产物的简单方法，从而无需高通量测序和复杂的数据分析即可确定命中的环状拟肽的结构。我们还开发了一种子库筛选策略，以在开始费力且不切实际的命中确认之前最大程度地减少由编码DNA标签的干扰引起的误报。鉴于合成和筛选的简单性和鲁棒性，