title: Design, synthesis, and diversification of ribosomally derived peptide macrocycles.
abstract: Ring topologies are widespread structural motifs among biologically active peptides found in nature. The recurrence of this motif is linked to the inherent advantages resulting from backbone cyclization, which include increased resistance against proteolytic degradation, improved cell permeability, and tighter and more specific interaction with the respective biomolecular target. Inspired by these natural product topologies, a number of groups have recently focused on developing methodologies that hinge upon the chemical elaboration of ribosomally derived polypeptides toward the synthesis and diversification of macrocyclic peptide structures. In this review, we highlight recent advances in this emerging new area and discuss the opportunities created by these methods toward the discovery of new functional entities.
authors.affiliation: Department of Chemistry, University of Rochester, Rochester, NY 14627, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Frost
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Smith
authors.forename: Rudi
authors.initials: R
authors.lastname: Fasan
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D047668:Inteins; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary; D012270:Ribosomes
chemical_list: D003432:Cross-Linking Reagents; D010456:Peptides, Cyclic