Construction and screening of vast libraries of natural product-like macrocyclic peptides using in vitro display technologies

被引：63
|
作者：
Bashiruddin, Nasir K. [1 ]
Suga, Hiroaki [1 ]
机构：
[1] Univ Tokyo, Dept Chem, Grad Sch Sci, Tokyo 1130033, Japan
来源：
CURRENT OPINION IN CHEMICAL BIOLOGY | 2015年 / 24卷
关键词：
RIBOSOMAL SYNTHESIS; CYCLIC-PEPTIDES; STRUCTURAL BASIS; TRANSLATION INITIATION; SELECTION; INHIBITORS; DISCOVERY; COCRYSTALLIZATION; DEACETYLASE; FLEXIZYMES;
D O I：
10.1016/j.cbpa.2014.11.011
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：
Macrocyclic structure and backbone N-methylation represent characteristic features of peptidic natural products, which play critical roles in their biological activity. Although natural products have been the traditional source of such peptides, recent developments in synthesizing natural product-like macrocyclic peptides using reconstituted translation systems have enabled us to construct vast trillion-member libraries of non-standard macrocyclic peptides. In addition, a method for displaying such libraries on their corresponding mRNA templates allows us to rapidly screen them for potent ligands against various drug targets. This review describes methodologies for the ribosomal synthesis of novel natural product-like macrocyclic peptides and their recent applications in the discovery of bioactive molecules using in vitro display technologies.
引用
收藏
页码：131 / 138
页数：8
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