title: Selection-based discovery of druglike macrocyclic peptides.
abstract: Macrocyclic peptides are an emerging class of therapeutics that can modulate protein-protein interactions. In contrast to the heavily automated high-throughput screening systems traditionally used for the identification of chemically synthesized small-molecule drugs, peptide-based macrocycles can be synthesized by ribosomal translation and identified using in vitro selection techniques, allowing for extremely rapid (hours to days) screening of compound libraries comprising more than 10(13) different species. Furthermore, chemical modification of translated peptides and engineering of the genetic code have greatly expanded the structural diversity of the available peptide libraries. In this review, we discuss the use of these technologies for the identification of bioactive macrocyclic peptides, emphasizing recent developments.
authors.affiliation: Department of Chemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan; email: toby@chem.s.u-tokyo.ac.jp , katoh@chem.s.u-tokyo.ac.jp , y-goto@chem.s.u-tokyo.ac.jp , hsuga@chem.s.u-tokyo.ac.jp.
authors.forename: Toby
authors.initials: T
authors.lastname: Passioura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Katoh
authors.forename: Yuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suga
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005815:Genetic Code; D057166:High-Throughput Screening Assays; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D014176:Protein Biosynthesis; D015202:Protein Engineering / Q000379:methods; D025941:Protein Interaction Mapping / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry
chemical_list: D019151:Peptide Library; D010455:Peptides; D012333:RNA, Messenger
keywords: flexizyme; genetic code expansion; genetic code reprogramming; mRNA display; phage display