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

被引：51

作者：

Ito, Kenichiro ^{[1
]}

Passioura, Toby ^{[1
]}

Suga, Hiroaki ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Sci, Dept Chem, Bunkyo Ku, Tokyo 1130033, Japan

来源：

MOLECULES | 2013年 / 18卷 / 03期

关键词：

non-standard macrocyclic peptides; non-canonical amino acids; flexizyme; Random non-standard Peptide Integration Discovery (RaPID) system; peptide inhibitors; IN-VITRO SELECTION; UNNATURAL AMINO-ACIDS; CYCLIC-PEPTIDES; RIBOSOMAL SYNTHESIS; GENETIC-CODE; TRANSLATION INITIATION; BICYCLIC PEPTIDES; DRUG DISCOVERY; N-METHYLATION; DE-NOVO;

D O I：

10.3390/molecules18033502

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (>10(12)), 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.

引用

页码：3502 / 3528

页数：27

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