On the basis of computational design, a focused one-bead one-compound library has been prepared on microparticle-encoded PEGA1900 beads consisting of small tripeptides with a triazole-capped N-terminal. The library was screened towards a double point-mutated version of the human FKBP12 protein, known as the destabilizing domain (DD). Inspired by the decoded library hits, unnatural peptide structures were screened in a novel on-bead assay, which was useful for a rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure refinement was accomplished using small quantities of library building blocks.

中文翻译：

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结合不稳定的FKBP12的Shield-1肽模拟物的设计和组合开发。

在计算设计的基础上，已针对由小三肽和三唑封端的N末端组成的微粒编码的PEGA1900珠制备了聚焦的单珠单化合物文库。针对人FKBP12蛋白的双点突变版本（称为去稳定结构域（DD））筛选了该文库。受解码的文库命中率的启发，在新颖的珠上检测方法中筛选了非天然肽结构，这对于在离珠重新合成之前进行快速结构评估很有用。随后，制备了19种化合物，并使用竞争荧光偏振分析法进行了测试，这导致发现了对DD具有低微摩尔结合亲和力的肽配体。该方法代表了一种鉴定新型结构支架的快速方法，