Sitting on the interface between biologics and small molecules, peptides represent an emerging class of therapeutics. Numerous techniques have been developed in the past 30 years to take advantage of biological methods to generate and screen peptide libraries for the identification of therapeutic compounds, with phage display being one of the most accessible techniques. Although traditional phage display can generate billions of peptides simultaneously, it is limited to expression of canonical amino acids. Recently, several groups have successfully undergone efforts to apply genetic code expansion to introduce noncanonical amino acids (ncAAs) with novel reactivities and chemistries into phage-displayed peptide libraries. In addition to biological methods, several different chemical approaches have also been used to install noncanonical motifs into phage libraries. This review focuses on these recent advances that have taken advantage of both biological and chemical means for diversification of phage libraries with ncAAs.

中文翻译：

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通过非规范氨基酸诱变和化学修饰实现噬菌体展示肽库的多样化

肽位于生物制剂和小分子之间的界面，代表了一类新兴的治疗方法。在过去的 30 年里，已经开发了许多技术来利用生物方法来生成和筛选肽库来鉴定治疗化合物，其中噬菌体展示是最容易获得的技术之一。尽管传统的噬菌体展示可以同时产生数十亿个肽，但其仅限于经典氨基酸的表达。最近，几个小组成功地尝试应用遗传密码扩展，将具有新颖反应性和化学性质的非规范氨基酸（ncAA）引入噬菌体展示的肽库中。除了生物学方法之外，还使用了几种不同的化学方法将非规范基序安装到噬菌体文库中。本综述重点关注利用生物和化学手段使 ncAA 噬菌体库多样化的最新进展。