title: Construction and screening of vast libraries of natural product-like macrocyclic peptides using in vitro display technologies.
abstract: 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Nasir K
authors.initials: NK
authors.lastname: Bashiruddin
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: hsuga@chem.s.u-tokyo.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010452:Peptide Biosynthesis; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: D001688:Biological Products; D047028:Macrocyclic Compounds; D019151:Peptide Library; D010456:Peptides, Cyclic