Mirror-image proteins and peptides composed of D-amino acids are garnering increasing attention as diagnostic agents and drug candidates due to their higher stability and lower immunogenicity compared with their L-amino acid counterparts. The often-used strategy to discover mirror-image protein and peptide ligands of a native protein is the mirror-image phage display technique, in which the D-enantiomeric form of the L-target is used as the bait in phage display screening. Advancements in chemical protein synthesis have greatly facilitated the production of these D-protein targets, which are unattainable through recombinant expression technologies. This review spotlights recent developments in mirror-image protein and peptide drugs, focusing on the state-of-the-art synthetic methodologies that have been employed to acquire D-protein targets as well as the basic workflow and recent progress of mirror-image phage display and its applications to drug discovery.

由 D-氨基酸组成的镜像蛋白和肽由于与 L-氨基酸对应物相比具有更高的稳定性和更低的免疫原性，作为诊断剂和候选药物而受到越来越多的关注。发现天然蛋白质的镜像蛋白和肽配体的常用策略是镜像噬菌体展示技术，其中L-靶标的D-对映体形式用作噬菌体展示筛选中的诱饵。化学蛋白质合成的进步极大地促进了这些 D 蛋白靶标的生产，这是通过重组表达技术无法实现的。本文重点介绍了镜像蛋白和多肽药物的最新进展，重点介绍了用于获取 D 蛋白靶标的最先进的合成方法以及镜像噬菌体的基本工作流程和最新进展显示及其在药物发现中的应用。