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Molecules 2013, 18(3), 3502-3528; doi:10.3390/molecules18033502

Technologies for the Synthesis of mRNA-Encoding Libraries and Discovery of Bioactive Natural Product-Inspired Non-Traditional Macrocyclic Peptides

Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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Received: 31 January 2013 / Revised: 4 February 2013 / Accepted: 25 February 2013 / Published: 18 March 2013
(This article belongs to the Special Issue Chemical Protein and Peptide Synthesis)
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Abstract

In this review, we discuss emerging technologies for drug discovery, which yields novel molecular scaffolds based on natural product-inspired non-traditional peptides expressed using the translation machinery. Unlike natural products, these technologies allow for constructing mRNA-encoding libraries of macrocyclic peptides containing non-canonical sidechains and N-methyl-modified backbones. The complexity of sequence space in such libraries reaches as high as a trillion (>1012), affording initial hits of high affinity ligands against protein targets. Although this article comprehensively covers several related technologies, we discuss in greater detail the technical development and advantages of the Random non-standard Peptide Integration Discovery (RaPID) system, including the recent identification of inhibitors against various therapeutic targets. View Full-Text
Keywords: non-standard macrocyclic peptides; non-canonical amino acids; flexizyme; Random non-standard Peptide Integration Discovery (RaPID) system; peptide inhibitors non-standard macrocyclic peptides; non-canonical amino acids; flexizyme; Random non-standard Peptide Integration Discovery (RaPID) system; peptide inhibitors
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Ito, K.; Passioura, T.; Suga, H. Technologies for the Synthesis of mRNA-Encoding Libraries and Discovery of Bioactive Natural Product-Inspired Non-Traditional Macrocyclic Peptides. Molecules 2013, 18, 3502-3528.

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