Department of Chemistry and Division of Advanced Material Science, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea.
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea.
Bioorg Med Chem. 2021 Oct 15;48:116423. doi: 10.1016/j.bmc.2021.116423. Epub 2021 Sep 21.
Here we describe the design and synthesis of a DNA-encoded library of bicyclic peptoids. We show that our solid-phase strategy is facile and DNA-compatible, yielding a structurally diverse combinatorial library of bicyclic peptoids of various ring sizes. We also demonstrate that affinity-based screening of a DNA-encoded library of bicyclic peptoids enables to efficiently identify high-affinity ligands for a target protein. Given their highly constraint structures, as well as increased cell permeability and proteolytic stability relative to native peptides, bicyclic peptoids could be an excellent source of protein capture agents. As such, our DNA-encoded library of bicyclic peptoids will serve as versatile tools that facilitate the generation of potent ligands against many challenging targets, such as intracellular protein-protein interactions.
在这里，我们描述了一个双环肽缩氨酸 DNA 编码文库的设计和合成。我们表明，我们的固相策略是简单和 DNA 兼容的，产生了各种环大小的双环肽缩氨酸的结构多样的组合文库。我们还证明，基于亲和力的双环肽缩氨酸 DNA 编码文库的筛选能够有效地鉴定靶蛋白的高亲和力配体。鉴于它们的高度约束结构，以及相对于天然肽增加的细胞通透性和蛋白水解稳定性，双环肽缩氨酸可能是蛋白质捕获剂的极好来源。因此，我们的双环肽缩氨酸 DNA 编码文库将作为通用工具，促进针对许多具有挑战性的靶标的有效配体的产生，例如细胞内蛋白质-蛋白质相互作用。
