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Updated: Mar 13, 2026

A Fast and Quantitative Method for Post-translational Modification and Variant Enabled Mapping of Peptides to Genomes
Published on: May 22, 2018
Discovery of de novo peptides by mRNA and RaPID displays with post-translational modification methods
1National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China; Department of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
Peptides have emerged as promising therapeutic agents due to their high target specificity and low toxicity. Recent advances in technologies for de novo peptide discovery have positioned them as attractive candidates for drug development. Among the leading platforms for screening large peptide libraries, mRNA display stands out for its unparalleled library size (>10¹² unique sequences) and its compatibility with genetic code reprogramming, enabling the generation of natural product-like peptides. However, the dependence on ribosomal translation and specific acyl-tRNAs imposes significant constraints on the accessible chemical space. This review highlights strategies that employ post-translational modifications (PTMs) to overcome these limitations, thereby greatly expanding peptide structural diversity. The successful identification of potent pseudo-natural product peptides through integrated PTM-mRNA display systems underscores the therapeutic potential of this approach.
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