Technologies for the Synthesis of MRNA-encoding Libraries and Discovery of Bioactive Natural Product-inspired Non-traditional Macrocyclic Peptides

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2013 Mar 20

PMID 23507778

Citations 18

Authors

Kenichiro Ito

Toby Passioura

Hiroaki Suga

Affiliations

Soon will be listed here.

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.

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