Next Article in Journal
Terminalia chebula Extract Protects OGD-R Induced PC12 Cell Death and Inhibits LPS Induced Microglia Activation
Next Article in Special Issue
Lanthanide-Mediated Dephosphorylation Used for Peptide Cleavage during Solid Phase Peptide Synthesis
Previous Article in Journal
Synthesis, Bioevaluation and Structural Study of Substituted Phthalazin-1(2H)-ones Acting as Antifungal Agents
Previous Article in Special Issue
Synthesis of Peptide Radiopharmaceuticals for the Therapy and Diagnosis of Tumor Diseases
Molecules 2013, 18(3), 3502-3528; doi:10.3390/molecules18033502
Review

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

,
 and *
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
* Author to whom correspondence should be addressed.
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)
Download PDF [1092 KB, uploaded 18 June 2014]

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.
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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Export to BibTeX |
EndNote


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.

View more citation formats

Related Articles

Article Metrics

Comments

Citing Articles

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert