Genetic code manipulation enables the ribosomal synthesis of peptide libraries bearing diverse nonproteinogenic amino acids, which can be applied to the discovery of bioactive peptides in combination with screening methodologies, such as mRNA display. Despite a tremendous number of successes in incorporation of l-α-amino acids with non-proteinogenic sidechain and N-methyl-l-α-amino acids into nascent peptide chain, d-, β-, and γ-amino acids have suffered from low translation efficiency. This obstacle has been hindering their integration into such peptide libraries. However, the use of engineered tRNAs, which is able to effectively recruit EF-Tu or/and EF-P, has recently made possible significant improvement of their incorporation efficiency into nascent peptide. This article comprehensively summarizes the advance in such a methodology and applications to the discovery of peptide ligands against target proteins of interest.

中文翻译：

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使用核糖体合成的非标准肽库开发生物活性折叠剂。

遗传密码操纵可实现携带多种非蛋白原性氨基酸的肽库的核糖体合成，结合筛选方法（例如mRNA展示）可将其应用于生物活性肽的发现。尽管成功的在掺入了巨大数量的升-α氨基与非蛋白原侧链和N-甲基氨基酸升-α-氨基酸到新生肽链，d-，β-和γ-氨基酸的翻译效率低。这一障碍一直在阻碍它们整合到这种肽库中。但是，使用能够有效募集EF-Tu或/和EF-P的工程化tRNA，最近已使它们掺入新生肽的效率大大提高。本文全面总结了这种方法的进展，并将其应用于针对目标靶蛋白的肽配体的发现。