研究人员建立了用于下一代信息存储的非生物肽，并将其应用于多种小分子合成的编码。肽基标签的化学稳定性允许使用钯介导的反应来有效合成具有广泛化学多样性和高纯度的肽编码库（PEL）。研究人员通过对碳酸酐酶IX和致癌蛋白靶点BRD4(1)和MDM2的亲和力选择，证明了从PEL中成功地重新发现小分子蛋白配体。总的来说，这项工作确立了非生物肽作为小分子合成编码的信息载体，并被用来发现蛋白质配体。
据介绍，在DNA中编码小分子信息已被用来加速发现治疗目标（如蛋白质）的配体。然而，基于寡核苷酸的编码被信息稳定性和密度的固有限制所阻碍。
附：英文原文
Title: Abiotic peptides as carriers of information for the encoding of small-molecule library synthesis
Author: Simon L. Rssler, Nathalie M. Grob, Stephen L. Buchwald, Bradley L. Pentelute
Issue&Volume: 2023-03-03
Abstract: Encoding small-molecule information in DNA has been leveraged to accelerate the discovery of ligands for therapeutic targets such as proteins. However, oligonucleotide-based encoding is hampered by inherent limitations of information stability and density. In this study, we establish abiotic peptides for next-generation information storage and apply them for the encoding of diverse small-molecule synthesis. The chemical stability of the peptide-based tag allows the use of palladium-mediated reactions to efficiently synthesize peptide-encoded libraries (PELs) with broad chemical diversity and high purity. We demonstrate the successful de novo discovery of small-molecule protein ligands from PELs by affinity selection against carbonic anhydrase IX and the oncogenic protein targets BRD4(1) and MDM2. Collectively, this work establishes abiotic peptides as carriers of information for the encoding of small-molecule synthesis, leveraged herein for the discovery of protein ligands.
DOI: adf1354
Source: https://www.science.org/doi/10.1126/science.adf1354